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 …

Reciprocal activation of leukocyte endothelial adhesion molecules in acute coronary syndromes. (2003 Sep)
reciprocal activation of leukocyte endothelial adhesion molecules in acute coronary syndromes . background : The acute coronary syndromes are associated with an intense inflammatory response and sustained leukocyte activation . This inflammatory state has been correlated with an adverse prognosis , but the source of this inflammation remains controversial , with evidence that it may arise either from the coronary vasculature or from the systemic endothelium . methods : levels of soluble cell adhesion molecules , and of their respective monocyte cell surface ligands , were measured in the peripheral serum of 21 patients presenting with acute coronary syndromes . soluble intercellular adhesion molecule 1 and soluble vascular cell adhesion molecule 1 were measured by enzyme linked immunosorbent assay and expression of the monocyte integrins cd11b ( Mac 1 ) and cd49d ( VLA 4 ) was measured by direct immunofluorescence using flow cytometry . results : High levels of the monocyte receptor cd11b ( 531 vs . 345 MFI , P 0 . 01 ) , and its soluble intercellular adhesion molecule 1 ( 329 vs . 232 ng / ml , P 0 . 01 ) , were noted in patients with acute coronary syndromes compared to healthy controls . conclusions : reciprocal activation of monocyte receptor ligands and endothelial adhesion molecules was found in the peripheral blood of patients with acute coronary syndromes . This may indicate a coordinated state of pro inflammatory upregulation with widespread activation of both leukocytes and endothelium and suggests a systemic rather …

Adhesion molecules in inflammatory diseases : insights from knockout mice. (2002 Oct)
adhesion molecules in inflammatory diseases : insights from knockout mice . leukocyte / endothelial cell adhesion molecules are essential mediators of both immune and inflammatory responses . however , their specific roles in the initiation and progression of inflammatory diseases remain largely undefined . The focus of our laboratory is the identification of the adhesion molecule interactions that mediate leukocyte recruitment and tissue damage during the development of rheumatoid arthritis , systemic lupus erythematosus , and psoriasis . For these studies , we use a basic genetic approach in mice , analyzing different gene targeted adhesion molecule mutants , or knockouts , in murine disease models . Our findings suggest that loss of intercellular adhesion molecule 1 significantly inhibits the development of arthritis and glomerulonephritis , while selectin deficiency results in accelerated development of joint and kidney inflammation . Our results also indicate that the beta2 integrins may play a key role in regulating the initiation of psoriasiform skin diseases .

Cloning of an inflammation specific phosphatidyl inositol linked form of murine vascular cell adhesion molecule 1. (1993 May)
cloning of an inflammation specific phosphatidyl inositol linked form of murine vascular cell adhesion molecule 1 . vascular cell adhesion molecule 1 ( vcam1 ) is a member of the immunoglobulin ( Ig ) superfamily which interacts with the integrin very late antigen 4 ( VLA4 ) . The vcam1 / VLA4 interaction mediates both adhesion and signal transduction and is thought to play an important role in inflammatory and immune responses in vivo . vcam1 cdnas cloned from mouse , rat , rabbit , and human libraries contain six , seven , or eight extracellular Ig like domains generated by alternate splicing , but to date shorter forms have not been found . We have cloned a novel cDNA encoding only the three N terminal domains of murine vcam1 followed by a unique C terminal tail generated by alternate splicing of a previously undescribed exon . This truncated form of murine vcam1 ( 3D vcam1 ) is expressed in COS cells as a functional adhesion molecule which is lost from the cell surface following treatment with phosphatidylinositol specific phospholipase C . 3D vcam1 is found only in endotoxin treated but not control murine and rat tissues . Thus in rodents alternate splicing of the vcam1 gene generates a unique truncated inflammation specific phosphatidylinositol linked form of vcam1 .

Vascular endothelial growth factor expression of intercellular adhesion molecule 1 ( ICAM 1 ) , vascular cell adhesion molecule 1 … (2001 May)
vascular endothelial growth factor expression of intercellular adhesion molecule 1 ( ICAM 1 ) , vascular cell adhesion molecule 1 ( VCAM 1 ) , and E selectin through nuclear factor kappa B activation in endothelial cells . vascular endothelial growth factor ( VEGF ) induces adhesion molecules on endothelial cells during inflammation . Here we examined the mechanisms underlying VEGF stimulated expression of intercellular adhesion molecule 1 ( ICAM 1 ) , vascular cell adhesion molecule 1 ( VCAM 1 ) , and E selectin in human umbilical vein endothelial cells . VEGF ( 20 ng / ml ) increased expression of ICAM 1 , VCAM 1 , and E selectin mrnas in a time dependent manner . these effects were significantly suppressed by Flk 1 / kinase insert domain containing receptor ( KDR ) antagonist and by inhibitors of phospholipase C , nuclear factor ( NF ) kappab , sphingosine kinase , and protein kinase C , but they were not affected by inhibitors of mitogen activated protein / extracellular signal regulated kinase kinase ( MEK ) 1 / 2 or nitric oxide synthase . unexpectedly , the phosphatidylinositol ( PI ) 3 kinase inhibitor wortmannin enhanced both basal and VEGF stimulated adhesion molecule expression , whereas insulin , a PI 3 kinase activator , suppressed both basal and VEGF stimulated expression . Gel shift analysis revealed that VEGF stimulated NF kappab activity . This effect was inhibited by phospholipase C , NF kappab , or protein kinase …

Endothelial growth factors VEGF and bFGF differentially enhance monocyte and neutrophil recruitment to inflammation. (2006 Jul)
endothelial growth factors VEGF and bFGF differentially enhance monocyte and neutrophil recruitment to inflammation . vascular endothelial growth factor ( VEGF ) and basic fibroblast growth factor ( bFGF ) are produced at sites of inflammation . previously , we demonstrated that bFGF enhances leukocyte recruitment and endothelial cell adhesion molecule ( CAM ) expression during inflammation . Here , we investigated the influence of VEGF during acute inflammation and whether VEGF and bFGF cooperate to modulate leukocyte recruitment . inflammation was induced in skin of rats by intradermal injection of inflammatory stimuli / VEGF / bFGF . migration of 51Cr monocytes and 111in polymorphonuclear leukocytes ( PMN ) to the dermal lesions and 125I anti CAM monoclonal antibody binding to the dermal vasculature were quantitated after 2 h . VEGF significantly enhanced tumor necrosis factor alpha ( TNF alpha ) induced monocyte recruitment by 39 / 16 and increased P selectin , E selectin , and intercellular CAM 1 expression by two to threefold over TNF alpha alone . however , recruitment of monocytes to TNF alpha interferon gamma ( IFN gamma ) and of PMN to all stimuli tested was not affected by VEGF . In contrast , bFGF enhanced recruitment of both leukocyte types to all stimuli tested . With the potent TNF alpha IFN gamma stimulus , in contrast to bFGF , VEGF did not enhance E selectin or ICAM 1 expression . bFGF , but not VEGF , increased the chemotactic activity for PMN in …

Expression of leukocyte adhesion molecules by mucosal mononuclear phagocytes in inflammatory bowel disease. (1991 Jan)
expression of leukocyte adhesion molecules by mucosal mononuclear phagocytes in inflammatory bowel disease . leukocyte adhesion molecules are important in cell cell interactions of the immune system . lymphocyte function associated antigen 1 ( cluster designation 11a ) mediates interactions between T cells and mononuclear phagocytes through its ligand , the intercellular adhesion molecule 1 ( CD54 ) , whereas complement receptors 3 ( CD 11b ) and 4 ( cd11c ) are involved in complement mediated phagocytosis . expression of CD11 molecules and intercellular adhesion molecule 1 was studied in colonic biopsy specimens from 20 patients with inflammatory bowel disease and 10 normal controls . In normal colon , few mononuclear phagocytes expressed lymphocyte function associated antigen 1 and intercellular adhesion molecule 1 at high densities . The major adhesion molecule was cd11c . Thus , the largest population of normal colonic mononuclear phagocytes was represented by quiescent , resident macrophages with likely phagocytic function . In inflammatory bowel disease , mononuclear phagocytes showed only a slight increase in cd11a expression and no significant change in expression of cd11b and cd11c . By contrast , the percentage of mononuclear phagocytes expressing intercellular adhesion molecule 1 was increased from 6 . 9 / 3 . 9 in controls to 69 . 2 / 12 . 8 in ulcerative colitis ( P less than 0 . 001 ) and to 45 . 7 / 22 . 8 in crohn s disease ( P less than 0 . 01 ) , showing …

Levels of expression of P selectin , E selectin , and intercellular adhesion molecule 1 in coronary atherectomy specimens from … (1997 Apr)
levels of expression of P selectin , E selectin , and intercellular adhesion molecule 1 in coronary atherectomy specimens from patients with stable and unstable angina pectoris . unstable angina occurs when atherosclerotic plaque ruptures . recent evidence suggests a role for inflammation in this process . leukocyte endothelial cell interactions are important in inflammation and are regulated by cell adhesion molecules . This study was designed to examine the vascular expression of cell adhesion molecules and cytokines in patients with unstable angina . directional coronary atherectomy was performed in patients with unstable and stable angina . expression of the cell adhesion molecules P selectin , E selectin , and intercellular adhesion molecule 1 in the tissue obtained was examined using immunohistochemistry . In addition , expression of the cytokines tumor necrosis factor alpha and interleukin 1beta , which participate in the regulation of cell adhesion molecule expression , was also examined . atherectomy specimens had significantly greater P selectin expression from patients with unstable angina than from patients with stable angina . P selectin expression was observed primarily on endothelial cells . there were no differences in any of the other factors between patients with unstable and stable angina . In addition , other clinical and angiographic variables were not associated with differential expression of any of the cell adhesion molecules or cytokines . these results indicate a possible role for P selectin in the process of unstable angina .

Modulation of cell adhesion molecule expression and function on human lung microvascular endothelial cells by inhibition of phosphodiesterases 3 and … (1998 Aug)
modulation of cell adhesion molecule expression and function on human lung microvascular endothelial cells by inhibition of phosphodiesterases 3 and 4 . 1 . expression of cell adhesion molecules ( CAM ) on the lung microvascular endothelium is believed to play a key role in the recruitment of leukocytes in pulmonary inflammation . moreover , regulation of CAM expression may be an important mechanism through which this inflammation may be controlled . experimental evidence has suggested that combined phosphodiesterase ( PDE ) 3 and 4 inhibitors increase cyclic AMP levels within cells greater than inhibition of either isoenzyme alone . In the present study we assessed the effect of combinations of rolipram ( PDE4 inhibitor ) , ORG 9935 ( PDE3 inhibitor ) and salbutamol ( beta agonist ) on CAM expression and neutrophil or eosinophil adhesion to human lung microvascular endothelial cells ( hlmvec ) . 2 . tumour necrosis factor alpha ( TNF alpha ) induced intercellular adhesion molecule ( ICAM ) 1 , vascular cell adhesion molecule ( VCAM ) 1 and E selectin expression were measured on hlmvec monolayers at 6 h by a specific elisa technique in the presence of different combinations of medium , rolipram , ORG 9935 and salbutamol . 3 . rolipram in combination with salbutamol , but neither agent alone , inhibited TNF alpha induced E selectin expression , whilst ICAM 1 and VCAM 1 expression were not affected . ORG 9935 had no significant effect on CAM expression alone . …

Intercellular adhesion molecule 1 is the major adhesion molecule expressed during schistosome granuloma formation. (1997 Jan)
intercellular adhesion molecule 1 is the major adhesion molecule expressed during schistosome granuloma formation . endothelial cell adhesion molecules play a key role in inflammation by initiating leukocyte trafficking . One of the most complex inflammatory responses is the formation of a cellular granuloma . expression of adhesion molecules during granuloma formation was investigated by using the murine host reaction to schistosome parasite eggs deposited in the liver as a model . By both immunohistochemistry and lymphocyte adhesion assays , the predominant interaction identified was between intercellular adhesion molecule 1 ( ICAM 1 ) and its cognate integrin , leukocyte functional antigen 1 ( LFA 1 ) . ICAM 1 expression on sinusoidal endothelium was induced when eggs were first deposited in the liver , peaked in parallel with granuloma size , and was downregulated with modulation of the granuloma . polyacrylamide beads coated with soluble parasite egg antigens could induce ICAM 1 expression on endothelial cells in vitro only in the presence of tumor necrosis factor alpha , a cytokine previously shown to be key to granuloma formation . A role for ICAM 1 in recruiting lymphocytes to the hepatic granuloma was also supported by the observation that lymphocytes preincubated with anti LFA 1 antibody did not bind to granulomas in tissue sections . while ICAM 1 is the predominant adhesion molecule in schistosome egg granuloma formation in wild type mice , when the ICAM 1 gene is knocked out , vascular cell adhesion molecule 1 is upregulated and …

Novel inhibitors of cytokine induced ikappabalpha phosphorylation and endothelial cell adhesion molecule expression show anti inflammatory effects in vivo. (1997 Sep)
novel inhibitors of cytokine induced ikappabalpha phosphorylation and endothelial cell adhesion molecule expression show anti inflammatory effects in vivo . We have identified two compounds that inhibit the expression of endothelial leukocyte adhesion molecules intercellular adhesion molecule 1 , vascular cell adhesion molecule 1 , and E selectin . these compounds act by inhibiting tumor necrosis factor alpha induced phosphorylation of ikappab alpha , resulting in decreased nuclear factor kappab and decreased expression of adhesion molecules . The effects on both ikappab alpha phosphorylation and surface expression of E selectin were irreversible and occurred at an IC50 of approximately 10 microm . these agents selectively and irreversibly inhibited the tumor necrosis factor alpha inducible phosphorylation of ikappab alpha without affecting the constitutive ikappab alpha phosphorylation . although these compounds exhibited other activities , including stimulation of the stress activated protein kinases , p38 and JNK 1 , and activation of tyrosine phosphorylation of a 130 140 kDa protein , these effects are probably distinct from the effects on adhesion molecule expression since they were reversible . One compound was evaluated in vivo and shown to be a potent anti inflammatory drug in two animal models of inflammation . The compound reduced edema formation in a dose dependent manner in the rat carrageenan paw edema assay and reduced paw swelling in a rat adjuvant arthritis model . these studies suggest that inhibitors of cytokine inducible ikappabalpha phosphorylation exert anti inflammatory activity in vivo .

Increased mucosal concentrations of soluble intercellular adhesion molecule 1 ( sicam 1 ) , sE selectin , and interleukin 8 … (1996 Oct)
increased mucosal concentrations of soluble intercellular adhesion molecule 1 ( sicam 1 ) , sE selectin , and interleukin 8 in active ulcerative colitis . Cell surface adhesion molecules ( CAM ) are important promotors of the immunoinflammatory cascade . The circulating levels of soluble intercellular adhesion molecule 1 ( ICAM 1 ) have previously been shown to correlate with disease activity in inflammatory bowel disease . The primary aim of this study was consequently to investigate if this also applies to mucosal levels of soluble ICAM 1 . We measured soluble ICAM 1 levels in intestinal biopsy specimens and the endoscopic activity of 69 patients with ulcerative colitis ( UC ) and 14 controls and found that the median concentration of soluble ICAM 1 was significantly higher in patients with moderately or very active UC ( 15 . 0 ng / ml ) as compared to slightly active ( 9 . 8 ng / ml ) and inactive UC ( 9 . 5 ng / ml ) as well as controls ( 6 . 5 ng / ml ) ( P 0 . 005 ) . To further elucidate the interactions , two other CAM E selectin and vascular cellular adhesion molecule 1 ( VCAM 1 ) , together with interleukin 8 ( IL 8 ) , IL 2 receptor ( IL 2R ) alpha and beta chains , were also measured . A significant trend towards higher soluble E selectin levels in biopsies with active UC ( 1 …

Lectin like cell adhesion molecule 1 mediates leukocyte rolling in mesenteric venules in vivo. (1991 Jul)
lectin like cell adhesion molecule 1 mediates leukocyte rolling in mesenteric venules in vivo . during the inflammatory response , granulocytes and other leukocytes adhere to and emigrate from small venules . before firm attachment , leukocytes are observed rolling slowly along the endothelium in venules of most tissues accessible to intravital microscopy . The molecular mechanism underlying this early type of leukocyte endothelial interaction is unknown . leukocyte rolling was investigated in venules ( diameter , 40 microns ) of the exposed rat mesentery . micro infusion of a recombinant soluble chimera ( LEC IgG ) of the murine homing receptor lectin like cell adhesion molecule 1 ( LEC CAM 1 ; gp90mel ) into individual venules reduced the number of rolling leukocytes by 89 / 2 ( mean / SEM , n 20 venules ) , while a similar CD4 chimera ( CD4 IgG ) had no effect ( inhibition 14 / 7 , n 25 ) . rolling was also greatly reduced by a polyclonal serum against LEC CAM 1 ( inhibition 84 / 3 , n 35 ) ; preimmune serum was ineffective ( 11 / 13 inhibition , n 28 ) . these findings indicate that LEC CAM 1 mediates the adhesive interaction underlying leukocyte rolling and thus may play an important role in inflammation and in pathologic conditions involving leukocytes .

Elevated cyclic AMP inhibits endothelial cell synthesis and expression of TNF induced endothelial leukocyte adhesion molecule 1 , and vascular … (1993 Jun)
elevated cyclic AMP inhibits endothelial cell synthesis and expression of TNF induced endothelial leukocyte adhesion molecule 1 , and vascular cell adhesion molecule 1 , but not intercellular adhesion molecule 1 . We have investigated the role of cAMP as a signal transducer for TNF induction of leukocyte adhesion molecule expression in cultured human umbilical vein endothelial cells ( EC ) . forskolin , a stimulator of adenylate cyclase , either alone or in combination with isobutyl methylxanthine ( IBMX ) , an inhibitor of phosphodiesterase , fails to induce expression of endothelial leukocyte adhesion molecule 1 ( ELAM 1 or E selectin ) , of vascular cell adhesion molecule 1 ( VCAM 1 ) or of intercellular adhesion molecule 1 ( ICAM 1 or CD54 ) . unexpectedly , this combination of cAMP elevating drugs inhibits TNF induction of ELAM 1 and VCAM 1 but not ICAM 1 expression . similar results were observed with the membrane permeant cAMP mimetics 8 bromoadenosine 3 : 5 cyclic monophosphate ( 8Br cAMP ) and N ( 6 ) 2 O dibutyryladenosine 3 : 5 cyclic monophosphate . inhibition was greater at lower TNF concentrations ( 10 U / ml ) , at higher 8 Br cAMP concentrations ( 100 microm ) , and at early times ( 2 h ) . forskolin plus IBMX selectively inhibits TNF induced increases in ELAM 1 and VCAM 1 mRNA , indicating that the action of cAMP is to block synthesis of these molecules . …

Identification of a murine ICAM 1 specific peptide by subtractive phage library selection on cells. (2003 Sep)
identification of a murine ICAM 1 specific peptide by subtractive phage library selection on cells . The ICAM 1 adhesion molecule is expressed selectively at low levels on endothelial cells but is strongly upregulated in dysfunctional endothelial cells associated with inflammation , cancer , and atherogenesis . using COS 7 cells transfected with murine ICAM 1 ( micam 1 ) as a target receptor , a phage display library was screened . clones were selected by elution with a mAb specific for a functional epitope of ICAM 1 and a novel peptide sequence binding to the extracellular domain of micam 1 was identified that can potentially be used as a targeting vector aimed at dysfunctional endothelium . We further showed that the targeting specificity of the peptide was retained following its incorporation at the N terminal end of a large chimeric protein . moreover , this chimeric protein containing the micam 1 specific sequence was found to inhibit ICAM 1 mediated intercellular adhesion during antigen presentation . taken together , these results demonstrate the potential for improving the cell selectivity and properties of therapeutical agents toward targeting adhesion molecules involved in cell cell interactions .

A novel role for interleukin 18 in adhesion molecule induction through NF kappa B and phosphatidylinositol ( PI ) 3 … (2001 Oct)
A novel role for interleukin 18 in adhesion molecule induction through NF kappa B and phosphatidylinositol ( PI ) 3 kinase dependent signal transduction pathways . interleukin 18 ( IL 18 ) is a novel proinflammatory cytokine found in serum and joints of patients with rheumatoid arthritis ( RA ) . We studied a novel role for IL 18 in mediating cell adhesion , a vital component of the inflammation found in RA and other inflammatory diseases . We examined the expression of cellular cell adhesion molecules E selectin , vascular cell adhesion molecule 1 ( VCAM 1 ) , and intercellular adhesion molecule 1 ( ICAM 1 ) on endothelial cells and RA synovial fibroblasts using flow cytometry . adhesion of the monocyte like cell line HL 60 to endothelial cells was determined by immunofluorescence . IL 18 significantly enhanced ICAM 1 and VCAM 1 expression on endothelial cells and RA synovial fibroblasts . In addition , IL 18 induced E selectin expression on endothelial cells and promoted the adhesion of HL 60 cells to IL 18 stimulated endothelial cells . neutralizing anti VCAM 1 and anti E selectin could completely inhibit HL 60 adherence to endothelial cells . IL 18 induced adhesion molecule expression appears to be mediated through nuclear factor kappa B ( NF kappa B ) and phosphatidyl inositol 3 kinase ( PI 3 kinase ) since addition of inhibitors to either NF kappa B ( pyrrolidine dithiocarbamate and N acetyl l cysteine ) or PI …

Angiocentric recruitment of lymphocytes into the lung after the intrabronchial instillation of antigen. (2000 Jun)
angiocentric recruitment of lymphocytes into the lung after the intrabronchial instillation of antigen . The pathogenesis of acute lymphocytic inflammation in the lower respiratory tract appears to involve the recruitment of lymphocytes out of the blood stream and into the extravascular lung tissue . To investigate the membrane molecules regulating this process , we used the intrabronchial instillation of cellular antigen to trigger lymphocyte recruitment into the lower respiratory tract . sheep presensitized 6 to 10 weeks earlier at a remote site were intrabronchially challenged with 1 5 x 10 ( 7 ) cells from a B lymphoblastoid cell line . The cells were instilled into a subsegmental bronchus through a bronchial catheter . The stimulated and contralateral control segments were studied at a peak of inflammation , approximately 72 hours after antigen stimulation . gross and microscopic studies of the stimulated segment demonstrated localized inflammation characterized by the perivascular infiltration of lymphocytes . In contrast , control areas of the lung demonstrated only scattered perivascular lymphocytes . immunohistochemistry of the stimulated lung showed that the majority of these perivascular cells were CD3 CD4 lymphocytes . The T lymphocytes expressed high levels of the cell adhesion molecules beta 1 integrin and LFA 1 , but low levels of the L selectin membrane molecule . immunohistochemistry of the endothelial cells associated with the lymphocyte infiltrates demonstrated intense staining of the ICAM 1 , and beta 1 integrin adhesion molecules . electron microscopic studies of the endothelial cells in the antigen stimulated …

Lymphocyte migration to inflamed lacrimal glands is mediated by vascular cell adhesion molecule 1 / alpha ( 4 ) beta … (2001 Aug)
lymphocyte migration to inflamed lacrimal glands is mediated by vascular cell adhesion molecule 1 / alpha ( 4 ) beta ( 1 ) integrin , peripheral node addressin / l selectin , and lymphocyte function associated antigen 1 adhesion pathways . sjogren s syndrome is an autoimmune disease characterized by inflammation and destruction of lacrimal and salivary glands . The development of the inflammation requires the migration of lymphocytes from the blood into these tissues . This migration involves multistep cascades with binding of lacrimal gland endothelial adhesion molecules to their ligands on circulating lymphocytes . We used nonobese diabetic mice , which develop autoimmune mediated lacrimal gland inflammation , as an experimental model to define the adhesion molecules that control lymphocyte migration into inflamed lacrimal glands . We found that vascular endothelia in inflamed areas of lacrimal gland expressed vascular cell adhesion molecule ( VCAM ) 1 and the peripheral node addressin ( PNAd ) , but not mucosal addressin cell adhesion molecule 1 . Most lymphocytes in the inflamed glands expressed alpha ( 4 ) integrin , L selectin , and lymphocyte function associated antigen ( LFA ) 1 . In vivo studies revealed that antibodies against VCAM 1 , alpha ( 4 ) integrin , PNAd , L selectin , or LFA 1 almost completely blocked lymphocyte migration from blood into inflamed lacrimal glands . there was no inhibition of migration by antibodies against mucosal addressin cell adhesion molecule 1 or alpha ( 4 ) beta ( …

Manassantin A and B isolated from saururus chinensis inhibit TNF alpha induced cell adhesion molecule expression of human umbilical vein … (2005 Mar)
manassantin A and B isolated from saururus chinensis inhibit TNF alpha induced cell adhesion molecule expression of human umbilical vein endothelial cells . leukocyte adhesion to the vascular endothelium is a critical initiating step in inflammation and atherosclerosis . We have herein studied the effect of manassantin A ( 1 ) and B ( 2 ) , dineolignans , on interaction of THP 1 monocytic cells and human umbilical vein endothelial cells ( huvec ) and expression of intercellular adhesion molecule 1 ( ICAM 1 ) , vascular cell adhesion molecule 1 ( VCAM 1 ) , and E selectin in huvec . When huvec were pretreated with 1 and 2 followed by stimulation with TNF alpha , adhesion of THP 1 cells to huvec decreased in dose dependent manner with IC50 values of 5 ng / mL and 7 ng / mL , respectively , without cytotoxicity . Also , 1 and 2 inhibited TNF alpha induced up regulation of ICAM 1 , VCAM 1 and E selectin . The present findings suggest that 1 and 2 prevent monocyte adhesion to huvec through the inhibition of ICAM 1 , VCAM 1 and E selectin expression stimulated by TNF alpha , and may imply their usefulness for the prevention of atherosclerosis relevant to endothelial activation .