IFN beta provides immuno protection in the retina by inhibiting ICAM 1 and cxcl9 in retinal pigment epithelial cells. (2008 Mar)
IFN beta provides immuno protection in the retina by inhibiting ICAM 1 and cxcl9 in retinal pigment epithelial cells . The retinal pigment epithelial ( RPE ) cell is a potent regulatory cell that facilitates normal physiologic processes and plays a critical role in a variety of retinal diseases . We evaluated IFN beta production in human RPE cells through TLR signaling and investigated the effects of IFN beta on RPE cells . RPE cells treated with poly ( I : C ) or infected with an RNA virus produce IFN beta . kinetic studies revealed that IFN beta levels continue to increase over a 48 h period and this was associated with the up regulation of IRF 7 gene expression , a known positive feedback molecule for IFN beta production . microarray analysis revealed that in IFN beta treated cells , 480 genes of 22 , 283 genes were up or down regulated by 2 fold . We hypothesize that IFN beta induction during TLR signaling in the retina is an immunosuppressive factor produced to limit immunopathologic damage . cytokine activation of RPE cells results in the production of the chemokines , cxcl9 and cxcl10 , and the adhesion molecule , ICAM 1 . pretreatment of RPE cells with IFN beta resulted in inhibition of ICAM 1 production and elimination of cxcl9 production . This treatment did not alter cxcl10 production . Anti IFN beta Ab blocked the inhibitory action of IFN beta . Real time PCR analysis revealed …

Endothelial adhesion molecules and their role in inflammation. (1993 Jul)
endothelial adhesion molecules and their role in inflammation . The emigration of leukocytes such as neutrophils into inflammatory sites requires adhesion to the endothelium of small venules . The initial adhesive event is margination characterized by rolling of neutrophils along the luminal surface of the endothelium . Each member of the selectin family of adhesion molecules has been shown to support neutrophil rolling under conditions of flow . E selectin is synthesized by endothelial cells following cytokine stimulation , P selectin is rapidly mobilized from weibel palade bodies to the endothelial cell surface following stimulation with agents such as histamine , and L selectin is constitutively expressed on the surface of leukocytes . Each selectin functions primarily as a lectin , recognizing carbohydrate structures on the leukocyte or endothelial cell surface . Once the marginated neutrophil forms a stationary adhesion with endothelial cells , it is stimulated by chemotactic factors to downregulate the selectin based adhesion and upregulate adherence dependent on beta 2 integrins , principally cd11a / CD18 ( LFA 1 ) and cd11b / CD18 ( Mac 1 ) . these adhesion molecules interact with intercellular adhesion molecule 1 ( ICAM 1 ) and possibly other structures on the endothelial cell , and the leukocyte rapidly emigrates into surrounding tissue . transendothelial migration in vitro is markedly inhibited by monoclonal antibodies against CD18 integrins or ICAM 1 . monoclonal antibodies against the selectins , CD18 , cd11a , cd11b , and ICAM 1 have all been shown to …

Role of intra cellular adhesion molecule 1 ( ICAM 1 ) and its soluble form ( sicam ) in chronic … (2004 Jun)
Role of intra cellular adhesion molecule 1 ( ICAM 1 ) and its soluble form ( sicam ) in chronic airway inflammation mucosal inflammation is the feature of both bronchial asthma and allergic rhinitis with evident of tissue eosinophilia , mast cells , eosinophils and T lymphocytes activation . The initial phase of cell recruitment is the margination and adhesion of leucocytes to the endothelium , prior to their transendothelial migration under a directed chemotactic stimulus . This adhesion occurs through specific ligand receptor couplets involving leucocyte endothelial adhesion molecules . One of these cell adhesion molecules is ICAM 1 , an important early marker of immune activation and response . Its ligand , leukocyte function associated antigen one ( LFA 1 ) is expressed on neutrophils , eosinophils and T cells . ICAM 1 was found to be expressed on epithelial and endothelial cells in rhinitis patients and in bronchial biopsies obtained from asthmatics also after allergen challenge . circulating forms of these adhesion molecules have been identified in the peripheral blood , bronchoalveolar lavage ( BAL ) fluid and nasal lavage in patients with asthma and rhinitis . systemic and local up regulation of sicam 1 suggests a function role for this soluble form of ICAM in the allergic inflammation .

Human / severe combined immunodeficient mouse chimeras. (1993 Apr)
human / severe combined immunodeficient mouse chimeras . An experimental in vivo model system to study the regulation of human endothelial cell leukocyte adhesion molecules . The ability of circulating white blood cells to enter inflamed tissues is mediated by specific cell adhesion molecules thought to be expressed in a programmed and sequential manner to form an adhesion cascade . because of the complexity of this process , it is becoming increasingly important to develop in vivo models . Two major problems have limited the utility of current animal models . The first is the inability of many of the antibodies developed against cell adhesion molecules in human cell culture models to cross react in animals . The second is the uncertainty in extrapolating animal ( particularly rodent ) findings to humans . To circumvent these problems , full thickness human skin grafts were transplanted onto immunodeficient ( severe combined immunodeficient ) mice . after 4 6 wk , the transplanted skin grafts closely resembled normal skin histologically and maintained their human vasculature as determined by immunohistochemical staining with human specific endothelial cell markers . intradermal injection of tumor necrosis factor alpha resulted in the reversible upregulation of the leukocyte endothelial adhesion molecules E selectin , vascular cell adhesion molecule 1 , and intercellular adhesion molecule 1 , and in an active inflammatory reaction with migration of murine leukocytes into cytokine injected areas . these results indicate that the severe combined immunodeficient mouse / human skin transplant model provides a …

Expression of cell adhesion molecules in the lungs of patients with idiopathic pulmonary fibrosis. (1995 Aug)
expression of cell adhesion molecules in the lungs of patients with idiopathic pulmonary fibrosis . idiopathic pulmonary fibrosis ( IPF ) is a chronic inflammatory disorder restricted to the lungs . leukocyte entry into the area of inflammation is regulated , at least partly , by endothelial expression of leukocyte selective cell adhesion molecules ( CAMs ) . To investigate the relevance of these CAMs to the accumulation of leukocytes in IPF , we examined the expression of E selectin ( endothelial leukocyte adhesion molecule 1 ; ELAM 1 ) , intercellular adhesion molecule 1 ( ICAM 1 ) , and vascular cell adhesion molecule 1 ( VCAM 1 ) by immunohistochemistry in lung tissue from nine patients with IPF and five nonsmoking normal subjects . The results demonstrated that in normal lungs , ICAM 1 was weakly expressed on endothelial cells , but neither E selectin nor VCAM 1 was detected . In the lungs of patients with IPF , E selectin expression on endothelial cells was restricted to honeycombing regions . endothelial expression of ICAM 1 was increased throughout the tissue , but VCAM 1 was not detected in IPF . The distribution of leukocytes in lungs with IPF consisted of mostly lymphocyte accumulation in the interstitium and neutrophil accumulation within the airspaces of honeycomb regions . these results suggest that E selectin may play a role in the recruitment of neutrophils in regions of honeycombing and that ICAM 1 may play a role in lymphocyte recruitment into …

Host defenses against disseminated candidiasis are impaired in intercellular adhesion molecule 1 deficient mice. (1996 Sep)
Host defenses against disseminated candidiasis are impaired in intercellular adhesion molecule 1 deficient mice . genetically engineered mice , which lack normal expression of intercellular adhesion molecule 1 ( ICAM 1 ) , were used to study the role of ICAM 1 in the host defense against disseminated candidiasis . The responses of ICAM 1 deficient mice and normal wild type mice were compared following an intravenous challenge with candida albicans . ICAM 1 deficient mice lost more weight ( P . 001 ) and had a significantly higher mortality ( P . 001 ) . quantitative cultures revealed a greater tissue fungal burden in ICAM 1 deficient mice compared with normal mice , in both the kidney ( P . 001 ) and the brain ( P . 007 ) . extensive inflammation , composed primarily of histiocytes admixed with lymphocytes and occasional neutrophils , was present in the renal tissue of ICAM 1 deficient mice ; this contrasted with a more localized and predominantly neutrophilic infiltrate in normal mice . This work suggests that the loss of ICAM 1 significantly impairs host defense against C . albicans , by impairing either neutrophil migration or phagocyte activation or both .

An inhibitor of ikappab kinase , BMS 345541 , blocks endothelial cell adhesion molecule expression and reduces the severity of … (2004 Mar)
An inhibitor of ikappab kinase , BMS 345541 , blocks endothelial cell adhesion molecule expression and reduces the severity of dextran sulfate sodium induced colitis in mice . objective : inflammatory bowel diseases such as ulcerative colitis and crohn s disease are characterized by chronic relapsing inflammation . The transcription of many of the proteins which mediate the pathogenesis in inflammatory bowel disease ( e . g . , tnfalpha , ICAM 1 , VCAM 1 ) is NF kappab dependent . ikappab kinase is critical in transducing the signal inducible activation of NF kappab and , therefore , represents a potentially promising target for the development of novel agents to treat inflammatory bowel disease and other inflammatory diseases . results : Here we show that BMS 345541 , a highly selective inhibitor of ikappab kinase , inhibited the tnfalpha induced expression of both ICAM 1 and VCAM 1 in human umbilical vein endothelial cells at the same concentration range as cytokine expression is inhibited in monocytic cells ( IC ( 50 ) congruent with 5 microm ) . against dextran sulfate sodium induced colitis in mice , BMS 345541 administered orally at doses of 30 and 100 mg / kg was effective in blocking both clinical and histological endpoints of inflammation and injury . conclusion : This represents the first example of an inhibitor of ikappab kinase with anti inflammatory activity in vivo and indicates that inhibitors of IkB kinase show the promise of being highly efficacious in inflammatory …

Effects of adipocyte derived cytokines on endothelial functions : implication of vascular disease. (2005 May)
effects of adipocyte derived cytokines on endothelial functions : implication of vascular disease . adipose tissue has recently emerged as an active endocrine organ that secretes a variety of metabolically important substances , collectively called adipocytokines or adipokines . In this review we summarize the effects of the adipokines leptin , adiponectin , and resistin on the vasculature and their potential role for pathogenesis of vascular disease . leptin is associated with arterial wall thickness , decreased vessel distensibility , and elevated C reactive protein ( CRP ) levels . leptin possesses procoagulant and antifibrinolytic properties , and it promotes thrombus and atheroma formation , probably through the leptin receptors by promoting vascular inflammation , proliferation , and calcification , and by increasing oxidative stress . research for development of pharmacologic antagonism for the leptin receptor is currently under way . adiponectin inhibits the expression of the adhesion molecules ICAM 1 , VCAM 1 , and P selectin . therefore , it interferes with monocyte adherence to endothelial cells and their subsequent migration to the subendothelial space , one of the initial events in the development of atherosclerosis . adiponectin also inhibits the transformation of macrophages to foam cells in vitro and decreases their phagocytic activity . resistin , discovered in 2001 , represents the newest of the adipokines and was named for its ability to promote insulin resistance . resistin increases the expression of the adhesion molecules VCAM 1 and ICAM 1 , up regulates the monocyte chemoattractant chemokine …

Soluble intercellular adhesion molecule 1 and risk of future ischemic stroke : a nested case control study from the bezafibrate … (2002 Sep)
soluble intercellular adhesion molecule 1 and risk of future ischemic stroke : a nested case control study from the bezafibrate infarction prevention ( BIP ) study cohort . background AND purpose : inflammation is considered to be involved in the pathogenesis of ischemic stroke . Our purpose was to assess the role of soluble intercellular adhesion molecule 1 ( sicam 1 ) concentration , a marker of inflammation , in predicting future ischemic stroke among patients at risk because of chronic coronary heart disease . methods : We obtained baseline serum samples from patients with chronic coronary heart disease enrolled in the bezafibrate infarction prevention trial ( n 3090 ) , which assessed the efficacy of bezafibrate in secondary prevention . using a prospective nested case control design , we measured baseline sicam 1 concentration in sera of patients who developed ischemic stroke during a mean follow up of 8 . 2 years ( cases , n 134 ) and in age and sex matched controls without any subsequent cardiovascular events ( n 134 ) . results : baseline serum concentrations of sicam 1 were significantly higher in cases compared with controls ( 379 versus 350 ng / mL , P 0 . 05 ) . sicam 1 concentration at the highest quartile ( 394 ng / mL ) was associated with significantly higher relative odds of ischemic stroke compared with the lower concentrations after adjustment for potential confounding variables ( relative odds , 2 . 1 ; 95 CI …

Cross talk between ICAM 1 and granulocyte macrophage colony stimulating factor receptor signaling modulates eosinophil survival and activation. (2008 Mar)
cross talk between ICAM 1 and granulocyte macrophage colony stimulating factor receptor signaling modulates eosinophil survival and activation . reversal of eosinophilic inflammation has been an elusive therapeutic goal in the management of asthma pathogenesis . In this regard , GM CSF is a primary candidate cytokine regulating eosinophil activation and survival in the lung ; however , its molecular mechanism of propagation and maintenance of stimulated eosinophil activation is not well understood . In this study , we elucidate those late interactions occurring between the GM CSF receptor and activated eosinophil signaling molecules . using coimmunoprecipitation with GM CSF stimulated eosinophils , we have identified that the GM CSF receptor beta chain ( gmrbeta ) interacted with ICAM 1 and Shp2 phosphatase , as well as slp76 and ADAP adaptor proteins . separate experiments using affinity binding with a tyrosine phosphorylated peptide containing an ITIM ( ICAM 1 residues 480 488 ) showed binding to Shp2 phosphatase and gmrbeta . however , the interaction of gmrbeta with the phosphorylated ICAM 1 derived peptide was observed only with stimulated eosinophil lysates , suggesting that the interaction of gmrbeta with ICAM 1 required phosphorylated Shp2 and / or phosphorylated gmrbeta . importantly , we found that inhibition of ICAM 1 in activated eosinophils blocked GM CSF induced expression of c fos , c myc , IL 8 , and TNF alpha . moreover , inhibition of ICAM 1 expression with either antisense oligonucleotide or an ICAM 1 blocking Ab effectively inhibited …

Relation of improvement in endothelium dependent flow mediated vasodilation after rosiglitazone to changes in asymmetric dimethylarginine , endothelin 1 , … (2006 Oct)
relation of improvement in endothelium dependent flow mediated vasodilation after rosiglitazone to changes in asymmetric dimethylarginine , endothelin 1 , and C reactive protein in nondiabetic patients with the metabolic syndrome . The mechanisms by which thiazolidinediones exert beneficial effects on the endothelium are still not clear . We examined the effects of rosiglitazone on the plasma markers of metabolic control ( glucose , insulin , adiponectin , resistin , and lipid profiles ) , markers of inflammation ( high sensitivity C reactive protein CRP , interleukin 6 , soluble CD40 ligand , intercellular adhesion molecule 1 , and vascular cell adhesion molecule 1 ) , and markers of vasoreactivity ( asymmetric dimethylarginine ADMA and endothelin 1 ) and analyzed the relations between changes in endothelium dependent flow mediated dilation of the brachial artery and changes in these markers to elucidate their roles in mediating the vascular protective effects of rosiglitazone . Of 70 nondiabetic patients who met a modified national cholesterol education program definition of the metabolic syndrome , 35 were randomized to receive rosiglitazone ( 4 mg / day ) and 35 to receive placebo for 8 weeks . At study end , treatment with rosiglitazone had significantly reduced plasma insulin ( 25 , p 0 . 004 ) and resistin ( 16 , p 0 . 001 ) , increased adiponectin ( 164 , p 0 . 001 ) , low density lipoprotein cholesterol ( 16 , p 0 . 005 ) , and apolipoprotein B ( …

Up regulation of C3 , C4 , and soluble intercellular adhesion molecule 1 co expresses with high sensitivity C reactive … (2004 Nov)
Up regulation of C3 , C4 , and soluble intercellular adhesion molecule 1 co expresses with high sensitivity C reactive protein in familial hypoalphalipoproteinaemia : further evidence of inflammatory activation . objective : To test the working hypothesis that inflammation underlying precocious and severe coronary atherosclerotic disease in familial hypoalphalipoproteinaemia ( FH ) can be mediated by up regulation of the innate immune response . methods AND results : 52 patients with FH were compared with 52 healthy controls with regard to immune system markers such as C reactive protein ( CRP ) , soluble intercellular adhesion molecule 1 ( sicam 1 ) , C3c , and C4 . patients differed from controls in their significantly lower concentrations of high density lipoprotein cholesterol ( 30 . 2 ( 4 . 0 ) v 50 . 5 ( 13 . 6 ) mg / dl , p 0 . 0001 ) and apolipoprotein A I ( 113 . 2 ( 19 . 9 ) v 148 . 7 ( 25 . 1 ) mg / dl , p 0 . 0001 ) and their higher triglyceride ( 139 . 3 ( 63 . 2 ) v 81 . 4 ( 41 . 7 ) mg / dl , p 0 . 0001 ) and CRP plasma concentrations ( median 0 . 33 mg / dl , range 0 . 02 4 . 66 mg / dl v median 0 . 07 mg / dl , range 0 . 02 0 . …

Expression of the adhesion molecules ICAM 1 , VCAM 1 , LFA 1 and VLA 4 in the skin is … (1999 Apr)
expression of the adhesion molecules ICAM 1 , VCAM 1 , LFA 1 and VLA 4 in the skin is modulated in progressing stages of chronic venous insufficiency . In inflammation and wound healing , dynamic changes in cell adhesion and migration are fundamental properties of the cells involved . disturbed interaction of leukocytes with microvascular endothelial cells has been proposed to be a central pathogenic factor in chronic venous insufficiency . This disease may therefore serve to elucidate dysregulated modulation of adhesion molecule expression in conditions of chronic inflammation and impaired wound healing . In this study , we determined how the expression of ICAM 1 / VCAM 1 on endothelial cells and their ligands LFA 1 / VLA 4 on leukocytes is modulated in skin of progressing stages of chronic venous insufficiency . immunohistochemical staining of skin biopsies revealed an increase in the expression of ICAM 1 and VCAM 1 on endothelial cells in an early stage of venous disease such as stasis dermatitis . Such protein expression correlated with an increase of corresponding mRNA in skin biopsies . expression of these CAMs on endothelial cells was accompanied by the occurrence of a marked perivascular infiltration of leukocytes , which expressed increased levels of LFA 1 and VLA 4 . In progressing stages of chronic venous insufficiency , characterized by hyperpigmentation and lipodermatosclerosis , which precede skin ulceration , all these CAMs remained upregulated on endothelial cells and infiltrating leukocytes . Our findings indicate that following an initial …

4 O methylgallic acid down regulates endothelial adhesion molecule expression by inhibiting NF kappab DNA binding activity. (2006 Nov)
4 O methylgallic acid down regulates endothelial adhesion molecule expression by inhibiting NF kappab DNA binding activity . We here investigated the functional effect of 4 O methylgallic acid ( 4 OMGA ) , a major metabolite of gallic acid abundant in red wine , on vascular inflammation and its action mechanism . 4 OMGA inhibited the expression of intercellular adhesion molecule 1 ( ICAM 1 ) and vascular cell adhesion molecule 1 ( VCAM 1 ) in human umbilical vein endothelial cells ( huvecs ) stimulated with tumor necrosis factor alpha ( TNF alpha ) , resulting in the suppression of leukocyte adhesion to huvecs . In addition , 4 OMGA inhibited the promoter activities of ICAM 1 and VCAM 1 and the activity of nuclear factor kappab ( NF kappab ) without affecting cytosolic ikappab kinase ( IKK ) activation , inhibitor of kappab ( ikappab ) phosphorylation and degradation , and nuclear translocation of NF kappab . This compound did not alter nitric oxide ( NO ) generation , but inhibited reactive oxygen species ( ROS ) production in TNF alpha stimulated huvecs , suggesting that NO and ROS are not involved in 4 OMGA mediated inhibition of NF kappab activity . moreover , 4 OMGA directly blocked the binding activity of NF kappab to its consensus DNA oligonucleotide , when pre incubated with the nuclear extract from TNF alpha stimulated huvecs , but not with the oligonucleotide alone . This inhibition was completely abolished by the …

Relationship of circulating biomarkers of inflammation and hemostasis with preclinical atherosclerotic burden in nonsmoking hypercholesterolemic men. (2006 Oct)
relationship of circulating biomarkers of inflammation and hemostasis with preclinical atherosclerotic burden in nonsmoking hypercholesterolemic men . background : relations of mediators of inflammation and hemostasis with preclinical atherosclerosis have been poorly analyzed . The aim of this study was to test potential associations of these blood markers with indicators of cardiovascular risk and atherosclerotic burden in asymptomatic , nonsmoking , hypercholesterolemic men . methods : A total of 87 men underwent cardiovascular risk assessment by means of 10 year framingham risk calculation ( median 9 ) and atherosclerotic burden evaluation by means of ultrasonographic measurement of common carotid intima media thickness and assessment of atherosclerotic plaques at three arterial sites ( three site plaques ) . results : Of the markers C reactive protein , tumor necrosis factor alpha , interleukin 10 , factor VIIc , fibrinogen , plasminogen activator inhibitor activator , soluble intercellular adhesion molecule 1 , soluble P selectin ( sP selectin ) , and von willebrand factor , only sP selectin was positively and independently associated with high framingham risk score ( 9 ) ( 71 . 7 / 3 . 6 ng / mL , n 33 v 59 . 6 / 2 . 8 , n 54 ; mean / SEM ; P . 05 ) and with three site plaques ( 75 . 4 / 5 . 7 ng / mL , n 14 v 62 . 0 / 2 . 5 , n 73 ; P . 05 ) . after …

Pathologic roles of prorenin and ( pro ) renin receptor in the eye. (2008 May)
pathologic roles of prorenin and ( pro ) renin receptor in the eye . recent reports indicated that tissue renin angiotensin system ( RAS ) was upregulated and angiotensin II type 1 receptor signaling plays crucial roles in ocular inflammation and neovascularization ; however , the precise mechanism for activating tissue RAS had not been defined until recently . ( Pro ) renin receptor , a recently identified molecule existing in the major organs but not in the circulation , has attracted growing attention as an activator of tissue RAS . When the handle region of the prorenin prosegment binds to ( pro ) renin receptor , prorenin undergoes a conformational change to its enzymatically active state without the conventional proteolysis of the prorenin prosegment . systemic treatment with a peptide with the structure of the handle region ( handle region peptide ; HRP ) , which competitively binds to ( pro ) renin receptor as a decoy peptide and inhibit the nonproteolytic activation of prorenin , resulted in the suppression of retinal inflammation and neovascularizaion in the rodent models . retinal expression of RAS related inflammatory and angiogenic molecules , such as intercellular adhesion molecule 1 , monocyte chemotactic protein 1 , and vascular endothelial growth factor , was also suppressed with application of HRP . these findings demonstrate that nonproteolytically activated prorenin plays a significant role in the ocular inflammation and neovascularization .

Transplanted neural precursor cells reduce brain inflammation to attenuate chronic experimental autoimmune encephalomyelitis. (2006 Apr)
transplanted neural precursor cells reduce brain inflammation to attenuate chronic experimental autoimmune encephalomyelitis . Stem cell transplantation was introduced as a mean of cell replacement therapy , but the mechanism by which it confers clinical improvement in experimental models of neurological diseases is not clear . Here , we transplanted neural precursor cells ( NPCs ) into the ventricles of mice at day 6 after induction of chronic experimental autoimmune encephalomyelitis ( EAE ) , a model of multiple sclerosis ( MS ) . transplanted cells migrated into white matter tracts and attenuated the clinical course of disease . NPC transplantation down regulated the inflammatory brain process at the acute phase of disease , as indicated by a reduction in the number of perivascular infiltrates and of brain CD3 T cells , an increase in the number and proportion of regulatory T cells and a reduction in the expression of ICAM 1 and LFA 1 in the brain . demyelination and acute axonal injury in this model are considered to result mainly from the acute inflammatory process and correlate well with the chronic neurological residua . In consequence to inhibition of brain inflammation , precursor cell transplantation attenuated the primary demyelinating process and reduced the acute axonal injury . As a result , the size of demyelinated areas and extent of chronic axonal pathology were reduced in the transplanted brains . We suggest that the beneficial effect of transplanted NPCs in chronic EAE is mediated , in part , by …

Expression of elastase and fibrin in venous leg ulcer biopsies : a pilot study of pentoxifylline versus placebo. (1996 Sep)
expression of elastase and fibrin in venous leg ulcer biopsies : a pilot study of pentoxifylline versus placebo . The pathogenesis of venous leg ulcers is based on the leakage of fibrinogen leading to a pericapillary fibrin cuff and plugging of capillaries by white blood cells . On the basis of a previous work , we had assumed that the key event in the pathogenesis of venous leg ulcers is related to inflammation generated by activated white blood cells that accumulate under unrelieved blood pressure , because in ulcer biopsies we had detected the presence of tumor necrosis factor alpha ( TNF alpha ) in intracapillary monocytes , elastase in the polymorphonuclear leukocytes near the vessels , and a pericapillary undegraded fibrin cuff causing a diffusion barrier to oxygen . This concept was developed because TNF alpha synthesized by activated monocytes is responsible for many deleterious effects . It has a potent mitogenic effect on fibroblasts , leading to new collagen deposition and angiogenesis , it induces an increase in collagenase production , it acts through upregulation of an intracellular adhesion molecule ( ICAM 1 ) , leading to leukocyte sequestration and consequently a release of toxic metabolites by the polymorphonuclear cells , an early step in chronic inflammation , it activates the coagulation pathway via a marked increase in monocyte associated tissue factor ( TF ) procoagulant activity , and it inhibits fibrinolysis by promoting the release of PAI 1 , contributing to undegraded fibrin deposition . therefore , …

Direct contact between human peripheral blood mononuclear cells and renal fibroblasts facilitates the expression of monocyte chemoattractant protein 1. (2003 Jul)
direct contact between human peripheral blood mononuclear cells and renal fibroblasts facilitates the expression of monocyte chemoattractant protein 1 . background : Cell to cell interaction is thought to be an important feature of a variety of biological processes . As far as the proinflammatory process is concerned , the interaction between mesangial cells and monocytes / macrophages induces the expression of monocyte chemoattractant protein 1 ( MCP 1 ) , and this may play a role in glomerulonephritis . In this study , we investigated whether the cell to cell interaction between immune cells and renal fibroblasts induces MCP 1 gene expression , which may be involved in interstitial inflammation in the kidney . methods : human renal fibroblast cell lines , tNKF ( from a normal kidney ) and tfkif ( from a kidney with fibrosis ) , and peripheral blood mononuclear cells ( PBMC ) were used to assess the effect of cell to cell contact on the expression of MCP 1 mRNA in the fibroblasts . The expression of the MCP 1 gene in the fibroblasts was also examined after stimulation with tumor necrosis factor alpha ( TNF alpha ) and the culture supernatant from PBMC . RT PCR was used to detect MCP 1 mRNA expression . neutralizing antibodies to intercellular adhesion molecule 1 ( ICAM 1 ) and vascular endothelial adhesion molecule 1 ( VCAM 1 ) were used to block the cell to cell contact between the fibroblasts and PBMC . results : …

Clinical and immunologic effects of a rush sublingual immunotherapy to parietaria species : A double blind , placebo controlled trial. (1999 Dec)
clinical and immunologic effects of a rush sublingual immunotherapy to parietaria species : A double blind , placebo controlled trial . background : The local ( noninjection ) routes of immunotherapy are presently regarded as viable therapeutic options for respiratory allergy , and their mechanisms of action are currently undergoing investigation . objective : We evaluated the clinical efficacy of a preseasonal rush sublingual swallow immunotherapy and its effects on allergic inflammation in patients with seasonal rhinoconjunctivitis caused by parietaria species . methods : thirty patients with parietaria species induced rhinoconjunctivitis ( 13 with mild intermittent asthma ) were randomly assigned sublingual swallow immunotherapy or placebo in a rush preseasonal course . We assessed the seasonal symptom drug intake score by diary card and the inflammatory infiltration and the intercellular adhesion molecule 1 expression on nasal epithelium after specific allergenic challenge before and after treatment . results : The investigated immunotherapy was well tolerated , and no side effects were recorded . A significant reduction of the symptom score ( P . 016 ) and drug intake score ( P . 008 ) after immunotherapy was observed only in the active group . A decrease of the cumulative score was observed also in the placebo group ( P . 046 ) , but the significance was clearly higher ( P . 006 ) in the active group . In the active group a reduction of neutrophils ( P . 001 ) , eosinophils ( P . 01 ) , and …