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 .

Blocking endothelial adhesion molecules : a potential therapeutic strategy to combat atherogenesis. (2004 Sep)
blocking endothelial adhesion molecules : a potential therapeutic strategy to combat atherogenesis . purpose OF review : This review provides a concise update of the involvement of endothelial adhesion molecules in atherogenesis , an overview of current advances in the development of adhesion molecule blocking agents , as well as an insight into the potential of these molecules in cardiovascular therapy . recent findings : As endothelial adhesion molecules are deemed to play an important role in the development and progression of atherosclerotic lesions , they are interesting targets for therapeutic intervention in this process . In particular , P selectin and vascular cell adhesion molecule 1 are widely considered to hold promise in this regard . current research efforts centre on the design of agents that directly block the interaction of the receptor with its ligand ( e . g . soluble P selectin glycoprotein ligand 1 , blocking antibodies , EWVD based peptides ) or that interfere with their synthesis ( e . g . antisense oligonucleotides ) or their regulatory control by nuclear factor kappa B or peroxisome proliferator activated receptor gamma . furthermore , adhesion molecules have been exploited as a target for the specific delivery of drug carriers ( e . g . biodegradable particles with entrapped dexamethasone ) or therapeutic compounds ( e . g . dexamethasone ) to the plaque . All approaches have been shown to be effective in blocking adhesion molecule function in in vitro studies and in vivo models for …

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 …

Transgenic mice expressing different levels of soluble platelet / endothelial cell adhesion molecule IgG display distinct inflammatory phenotypes. (1999 Dec)
transgenic mice expressing different levels of soluble platelet / endothelial cell adhesion molecule IgG display distinct inflammatory phenotypes . platelet / endothelial cell adhesion molecule 1 ( pecam 1 , CD31 ) , expressed on the surfaces of leukocytes and concentrated in the junctions between endothelial cells plays an important role in transendothelial migration of neutrophils and monocytes . soluble recombinant pecam IgG injected i . v . into mice blocks acute leukocyte emigration by 80 . To study the role of pecam in models of chronic inflammation , we generated transgenic mice constitutively expressing soluble full length murine pecam as an IgG chimera . three founder lines expressed this transgene and constitutively secreted murine pecam IgG into the plasma where it was maintained at characteristic concentrations for each line . All mice had similar hematologic profiles to wild type littermates and were healthy when maintained in the standard laboratory animal facility . Both the leukocytes and the endothelium of mice of all transgenic lines expressed the same levels of endogenous pecam 1 as wild type littermates . similarly , there were no detectable differences in the expression of several other common leukocyte and endothelial cell adhesion molecules . Mice that produced moderate ( 10 20 microg / ml ) concentrations of pecam IgG demonstrated a severely blunted acute inflammatory response , despite mobilizing appropriate numbers of circulating leukocytes . surprisingly , mice that constitutively produced high ( 400 1 , 000 microg / ml ) concentrations of pecam IgG …

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 …

Clostridium difficile toxin A induced microvascular dysfunction. (1994 Dec)
clostridium difficile toxin A induced microvascular dysfunction . Role of histamine . clostridium difficile toxin A ( Tx A ) mediates secretion and inflammation in experimental enterocolitis . intravital video microscopy was used to define the mechanisms that underlie the inflammatory reactions elicited by direct exposure of the microvasculature to Tx A . leukocyte adherence and emigration , leukocyte platelet aggregation , and extravasation of FITC albumin were monitored in rat mesenteric venules exposed to Tx A . significant increases in leukocyte adherence and emigration ( LAE ) and albumin leakage were noted within 15 30 min of Tx A exposure . these responses were accompanied by mast cell degranulation and the formation of platelet leukocyte aggregates . The Tx A induced increases in LAE and albumin leakage were significantly attenuated by pretreatment with either monoclonal antibodies ( mAbs ) directed against the leukocyte adhesion glycoproteins , CD11 / CD18 , intercellular adhesion molecule 1 , and P selectin ( but not E selectin ) or with sialyl lewis x , a counter receptor for P selectin . The mast cell stabilizer , lodoxamide , an H1 ( but not an H2 ) receptor antagonist , and diamine oxidase ( histaminase ) were also effective in reducing the LAE and albumin leakage elicited by Tx A . The platelet leukocyte aggregation response was blunted by an mAb against P selectin , sialyl lewis x , and the H1 receptor antagonist . these observations indicate that Tx A induces a leukocyte …

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 …

Role of angiotensin II type 1 receptor in the regulation of cellular adhesion molecules in atherosclerosis. (2001 Jul)
Role of angiotensin II type 1 receptor in the regulation of cellular adhesion molecules in atherosclerosis . background : inflammation is a central feature of coronary artery disease ( CAD ) that is characterized by increased expression of cellular adhesion molecules with the exception of L selectin . L selectin is a leukocyte adhesion molecule that is rapidly shed after leukocyte activation so that it appears to be decreased in CAD . The renin angiotensin system ( RAS ) is implicated in atherogenesis and up regulates these molecules . objectives : The aim of this study was to investigate the effect of angiotensin type 1 ( AT1 ) receptor antagonism on serum and leukocyte adhesion molecule expression in patients with CAD . blood samples were collected from 31 patients before and after 8 weeks of treatment with losartan ( 44 / 2 mg / d , mean / SE ) , an AT1 receptor antagonist . We measured serum intercellular adhesion molecule 1 , vascular cell adhesion molecule 1 , endothelial leukocyte adhesion molecule , and C reactive protein ( CRP ) . By flow cytometry , we also measured the expression of leukocyte cd11a , cd11b , cd11c , CD18 , CD31 , cd49d , and cd62l ( L selectin ) in 13 patients . results : treatment with losartan decreased systolic blood pressure ( 141 / 3 vs 135 / 4 mm Hg , P . 04 ) and increased plasma renin activity ( 1 . 2 / …

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 …

Endothelial inflammation and thrombolysis resistance in acute myocardial infarction. (2002 May)
endothelial inflammation and thrombolysis resistance in acute myocardial infarction . background : despite recent refinements to thrombolysis for acute myocardial infarction , a significant minority of patients still fail to reperfuse . there is no reliable predictor of this state of thrombolysis resistance , but platelet and endothelial factors are believed to be important . Cell adhesion molecules are expressed by the endothelium when activated and their shed or soluble portion can be quantified in the peripheral serum , where they may be taken as a measure of endothelial activation . We sought to find a link between markers of endothelial inflammation at time of infarction and failure to reperfuse as measured by vessel occlusion at angiography . methods : patients presenting with their first acute myocardial infarction had levels of soluble adhesion molecules , C reactive protein and monocyte chemotactic protein 1 measured prior to thrombolysis . An angiogram on day five after admission was performed to establish patency of the index vessel . results : levels of soluble vascular adhesion molecule 1 ( svcam 1 ) taken prethrombolysis were significantly elevated compared to those with a patent vessel ( 620 / 90 vs . 418 / 28 ng / ml , P 0 . 03 . The positive predictive value of svcam 1 for vessel patency was 88 . conclusions : We found elevated serum levels of the adhesion molecule soluble vascular adhesion molecule 1 ( svcam 1 ) at presentation in patients with acute myocardial infarction who …

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 …

Neutrophil platelet adhesion : relative roles of platelet P selectin and neutrophil beta2 ( DC18 ) integrins. (1998 Feb)
neutrophil platelet adhesion : relative roles of platelet P selectin and neutrophil beta2 ( DC18 ) integrins . neutrophils and platelets interact both physically and metabolically during inflammation and thrombosis , but the mechanisms responsible for their adhesion remain incompletely understood . neutrophil platelet adhesion was measured after specific stimulation of neutrophils , platelets , or both and quantified by flow cytometry . specific stimulation of either the neutrophil or the platelet led to a marked increase in the percentage of neutrophils that bound platelets , although platelet stimulation led to a large increase and neutrophil stimulation to only a small increase in the number of platelets per neutrophil . stimulation of both cells further increased the number of neutrophil platelet adhesive events and led to large numbers of platelets binding to each neutrophil . confirming previous observations , blocking antibodies to platelet P selectin ( cd62p ) partially inhibited adhesion . however , blockade of the neutrophil beta2 integrin cd11b / CD18 also inhibited the percentage of neutrophils that bound platelets . combining P selectin and cd11b / 18 blockade further inhibited the stimulated increase in the percentage of neutrophils binding platelets and the increased number of platelets per neutrophil . Both cell adhesion molecules were active even when only a single cell type was primarily activated , supporting physiologically important transcellular activation . these data suggest that : ( 1 ) neutrophil platelet adhesion can be initiated by specific activation of either the neutrophil or the platelet and …

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 .

Platelet endothelial cell adhesion molecule 1 ( pecam 1 ) and its interactions with glycosaminoglycans : 2. (2008 Apr)
platelet endothelial cell adhesion molecule 1 ( pecam 1 ) and its interactions with glycosaminoglycans : 2 . biochemical analyses . platelet endothelial cell adhesion molecule 1 ( pecam 1 ) ( CD31 ) , a member of the immunoglobulin ( Ig ) superfamily of cell adhesion molecules with six Ig like domains , has a range of functions , notably its contributions to leukocyte extravasation during inflammation and in maintaining vascular endothelial integrity . although pecam 1 is known to mediate cell adhesion by homophilic binding via domain 1 , a number of pecam 1 heterophilic ligands have been proposed . Here , the possibility that heparin and heparan sulfate ( HS ) are ligands for pecam 1 was reinvestigated . The extracellular domain of pecam 1 was expressed first as a fusion protein with the Fc region of human IgG1 fused to domain 6 and second with an N terminal Flag tag on domain 1 ( Flag pecam 1 ) . Both proteins bound heparin immobilized on a biosensor chip in surface plasmon resonance ( SPR ) binding experiments . binding was pH sensitive but is easily measured at slightly acidic pH . A series of pecam 1 domain deletions , prepared in both expression systems , were tested for heparin binding . This revealed that the main heparin binding site required both domains 2 and 3 . Flag pecam 1 and a Flag protein containing domains 1 3 bound HS on melanoma cell surfaces , but a …

Selective regulation of intercellular adhesion molecule 1 expression by interleukin 18 and interleukin 12 on human monocytes. (2003 Nov)
selective regulation of intercellular adhesion molecule 1 expression by interleukin 18 and interleukin 12 on human monocytes . induction of expression of adhesion molecules is a crucial step in inflammation . The role of interleukin 18 ( IL 18 ) in induction of various adhesion molecules was investigated in freshly isolated peripheral blood mononuclear cells and human monocyte and T cell lines . IL 18 selectively up regulated intercellular adhesion molecule 1 ( ICAM 1 ) expression on freshly isolated human monocytes , but not on lymphocytes . The expression of other adhesion molecules was not influenced . induction of ICAM 1 by IL 18 was dependent on endogenous tumour necrosis factor alpha ( TNF alpha ) , and IL 12 had an additive effect on that of IL 18 . No changes in adhesion molecule expression were observed on the monocytic cell line THP 1 and on the T cell lines HSB 2 and jurkat J16 . In addition , induction of ICAM 1 on monocytes by lipopolysaccharide was slightly , but significantly , inhibited by blockade of either endogenous IL 18 or TNF alpha with IL 18 binding protein or TNF binding protein , respectively . blocking IL 1 effects with IL 1 receptor antagonist did not influence ICAM 1 levels . In conclusion , IL 18 selectively up regulates the expression of ICAM 1 on monocytes , and this contributes to the proinflammatory effects of this cytokine .

A journey with platelet P selectin : the molecular basis of granule secretion , signalling and cell adhesion. (2001 Aug)
A journey with platelet P selectin : the molecular basis of granule secretion , signalling and cell adhesion . P selectin is a transmembrane protein that resides within the alpha granule membrane of unstimulated platelets . The extracellular domains face into the lumen of the granule and the cytoplasmic tail extends into the platelet cytoplasm . Upon platelet stimulation , P selectin is phosphorylated and translocated to the plasma membrane via a secretory pathway . P selectin in the plasma membrane surface is exposed and serves as a cell adhesion receptor to interact with other cell receptors , including PSGL 1 and GPIb . P selectin upregulates tissue factor in monocytes and leads to leukocyte accumulation in areas of vascular injury associated with thrombosis and inflammation .