Integrin activation by talin. (2005 Aug)
integrin activation by talin . The development and integrity of the cardiovascular system depends on integrins , a family of adhesion receptors , vitally important for homeostasis of animal species from fruit fly to man . integrins are critical players in cell migration , cell adhesion , cell cycle progression , differentiation , and apoptosis . consequently , integrins have a major impact on the patterning and functions of the blood and cardiovascular system . integrins undergo conformational changes , which alter their affinity for ligands through a process operationally defined as integrin activation . integrin activation is important for platelet aggregation , leukocyte extravasation , and cell adhesion and migration , thus influencing such processes as hemostasis , inflammation and angiogenesis . recently , a series of studies have begun to define the mechanism of integrin activation by demonstrating that binding of a cytoskeletal protein , talin , to integrin beta subunit cytoplasmic tail is a last common step in integrin activation . these findings indicate that talin is likely to be at the center of converging signaling pathways regulating integrin activation .

Hydrogen peroxide augments eosinophil adhesion via beta2 integrin. (2000 Dec)
hydrogen peroxide augments eosinophil adhesion via beta2 integrin . during eosinophil ( EOS ) accumulation at sites of allergic inflammation , an initial step is the binding of EOS to adhesion molecules expressed on vascular endothelial cells ( EC ) . We have previously observed that adhesion of peripheral blood EOS to recombinant human vascular cell adhesion molecule 1 ( rh VCAM 1 ) stimulates the respiratory burst of EOS . although the biological consequence of this activation remains to be elucidated , reactive oxygen species such as hydrogen peroxide ( H2O2 ) may modify the adhesive property of EOS . In the present study , we examined whether H2O2 modifies the adhesive property of EOS . EOS were isolated from the peripheral blood of healthy subjects . adhesion of the EOS to paraformaldehyde fixed human umbilical vein EC ( huvec ) , stimulated or not stimulated with tumour necrosis factor alpha ( TNF alpha ; 100 pM for 24 hr ) , was examined in the presence or absence of H2O2 . H2O2 significantly enhanced adhesion of EOS to both resting and TNF alpha stimulated fixed huvec ( P 0 . 01 , respectively ) . Such enhancing effects were inhibited by anti beta2 integrin antibody or anti cd11b antibody , but not by anti cd11a or anti alpha4 integrin antibody . H2O2 also enhanced EOS adhesion to rh intracellular cell adhesion molecule 1 ( ICAM 1 ) but not to rh VCAM 1 . finally , H2O2 enhanced …

Binding of paxillin to the alpha 9 integrin cytoplasmic domain inhibits Cell spreading. (2001 Oct)
binding of paxillin to the alpha 9 integrin cytoplasmic domain inhibits Cell spreading . alpha ( 9 ) beta ( 1 ) integrin is a member of the beta ( 1 ) integrin family , plays an important role in extravasation of neutrophils at sites of acute inflammation , and is required for the normal development of the lymphatic system . The alpha ( 9 ) and alpha ( 4 ) integrin subunits are most closely related and form a subfamily of integrin alpha subunits . previously , we have reported that the alpha ( 4 ) cytoplasmic domain directly and tightly binds paxillin , an intracellular signaling adaptor molecule . This interaction accounts for some of the unusual functional responses to alpha ( 4 ) integrin mediated cell adhesion , including stimulation of cell migration and inhibition of cell spreading and focal adhesion formation . In the current studies , we have examined the interaction between the alpha ( 9 ) cytoplasmic domain and paxillin . Here we report that the alpha ( 9 ) cytoplasmic domain binds paxillin directly and tightly and that the alpha ( 9 ) paxillin association inhibits cell spreading . We have identified amino acid residues in the alpha ( 9 ) cytoplasmic domain , Trp ( 999 ) and Trp ( 1001 ) , that are critical for paxillin binding , and alanine substitution of either Trp ( 999 ) or Trp ( 1001 ) blocks paxillin binding . furthermore , these mutations …

Role of primary and secondary capture for leukocyte accumulation in vivo. (1998 Feb)
Role of primary and secondary capture for leukocyte accumulation in vivo . leukocyte accumulation during inflammation depends on the concerted action of selectin and integrin adhesion molecules , which promote capture , rolling , and arrest of these cells on activated endothelium . In addition to interacting with endothelial cells , leukocytes can also adhere to already adherent leukocytes through an L selectin dependent mechanism . initiation of adhesion through this mechanism has been called nucleation and leads to characteristic geometric patterns ( ie , clusters and strings ) of adherent leukocytes in flow chambers . We have used intravital microscopy of tumor necrosis factor alpha ( TNF alpha ) treated mouse cremaster muscles to quantitatively investigate the potential role of leukocyte leukocyte adhesion in initiating and maintaining the leukocyte clusters that are commonly observed in inflamed venules . Our data show that in TNF alpha treated venules with diameters between 23 and 108 microm , leukocyte adhesion occurs in clusters that are 19 to 50 microm long and 8 to 44 microm wide . They are almost entirely made up of slow rolling leukocytes . Of all leukocytes recruited into a cluster ( 100 ) , the majority enter the cluster rolling along the endothelium and sharply reduce their velocity in the absence ( 59 ) or presence ( 15 ) of other leukocytes in proximity ( one cell diameter ) . Some of the rolling leukocytes ( 17 ) pass through the cluster without reducing their velocity . …

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 …

The extracellular matrix protein mindin serves as an integrin ligand and is critical for inflammatory cell recruitment. (2005 Nov)
The extracellular matrix protein mindin serves as an integrin ligand and is critical for inflammatory cell recruitment . leukocyte recruitment to inflammation sites depends on interactions between integrins and extracellular matrix ( ECM ) . In this report we show that mice lacking the ECM protein mindin exhibit severely impaired recruitment of neutrophils and macrophages in 4 different inflammation models . furthermore , neutrophils directly bind to immobilized mindin , and mindin matrix mediates neutrophil migration in vitro . The adhesion of neutrophils to mindin is blocked by anti integrin alpha4 , anti integrin alpha ( M ) , and anti integrin beta2 antibodies . We also show that HEK 293 cells transfected with cDNA encoding these integrins exhibit enhanced binding to immobilized mindin matrix and the increased binding can be blocked by anti integrin antibodies . Our results suggest that mindin serves as a novel ligand for integrins and mindin integrin interactions are critical for inflammatory cell recruitment in vivo .

Regulation of integrin function by the urokinase receptor. (1996 Sep)
regulation of integrin function by the urokinase receptor . integrin function is central to inflammation , immunity , and tumor progression . The urokinase type plasminogen activator receptor ( uPAR ) and integrins formed stable complexes that both inhibited native integrin adhesive function and promoted adhesion to vitronectin via a ligand binding site on uPAR . interaction of soluble uPAR with the active conformer of integrins mimicked the inhibitory effects of membrane uPAR . Both uPAR mediated adhesion and altered integrin function were blocked by a peptide that bound to uPAR and disrupted complexes . these data provide a paradigm for regulation of integrins in which a nonintegrin membrane receptor interacts with and modifies the function of activated integrins .

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 / …

Bioactive hydrogel substrates : probing leukocyte receptor ligand interactions in parallel plate flow chamber studies. (2006 Nov)
bioactive hydrogel substrates : probing leukocyte receptor ligand interactions in parallel plate flow chamber studies . The binding of activated integrins on the surface of leukocytes facilitates the adhesion of leukocytes to vascular endothelium during inflammation . interactions between selectins and their ligands mediate rolling , and are believed to play an important role in leukocyte adhesion , though the minimal recognition motif required for physiologic interactions is not known . We have developed a novel system using poly ( ethylene glycol ) ( PEG ) hydrogels modified with either integrin binding peptide sequences or the selectin ligand sialyl lewis X ( SLe ( X ) ) within a parallel plate flow chamber to examine the dynamics of leukocyte adhesion to specific ligands . The adhesive peptide sequences arginine glycine aspartic acid serine ( RGDS ) and leucine aspartic acid valine ( LDV ) as well as sialyl lewis X were bound to the surface of photopolymerized PEG diacrylate hydrogels . leukocytes perfused over these gels in a parallel plate flow chamber at physiological shear rates demonstrate both rolling and firm adhesion , depending on the identity and concentration of ligand bound to the hydrogel substrate . This new system provides a unique polymer based model for the study of interactions between leukocytes and endothelium as well as a platform to develop improved scaffolds for cardiovascular tissue engineering .

A role for platelets and endothelial selectins in tumor necrosis factor alpha induced leukocyte recruitment in the brain microvasculature. (2000 Dec)
A role for platelets and endothelial selectins in tumor necrosis factor alpha induced leukocyte recruitment in the brain microvasculature . The mechanisms mediating leukocyte recruitment into the cerebral nervous system during inflammation are still poorly understood . The objective of this study was to investigate the leukocyte recruitment in the brain microcirculation by intravital microscopy . superfusion of the brain with artificial cerebrospinal fluid did not induce leukocyte rolling or adhesion . however , intraperitoneal tumor necrosis factor alpha ( TNF alpha ) caused marked leukocyte rolling and adhesion in the brain microcirculation . histology revealed that the recruitment was primarily of neutrophils . Both E and P selectin were required for TNF alpha induced leukocyte recruitment , as rolling was reduced after treatment with either anti E or anti P selectin antibody and eliminated in E or P selectin deficient mice . A significant increase in brain P and E selectin expression was seen after TNF alpha treatment , but both were an order of magnitude less than in any other tissue . We observed significant platelet paving of TNF alpha stimulated endothelium and found that anti platelet antibody reduced leukocyte rolling and adhesion , as did acetylsalicylic acid ( aspirin ) . however , depletion of platelets did not reduce cerebral P selectin expression . moreover , chimeric mice lacking P selectin on endothelium but not platelets had significantly decreased P selectin expression and reduced leukocyte recruitment in the brain . This suggests a role for endothelial P …

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 …

Fatalities in natalizumab treatment a no go for leukocyte recirculation approaches ? natalizumab ( tysabri ) , biogen Idec / … (2006 Jul)
fatalities in natalizumab treatment a no go for leukocyte recirculation approaches ? natalizumab ( tysabri ) , biogen Idec / Elan ) is a humanised neutralising antibody directed against alpha4 integrin expressed by leukocytes . although it is an effective therapy for multiple sclerosis ( MS ) , the serious adverse effect of progressive multifocal leukoencephalopathy ( PML ) resulted in its voluntary withdrawal from the market by biogen Idec / Elan in february 2005 . This has raised debates on whether PML was caused by blocking leukocyte trafficking mediated immune suppression or by other effects through targeting alpha4 integrin per se . The authors propose that natalizumab associated PML is a target specific side effect predominantly due to the combination of : i ) blocking leukocyte trafficking to peripheral organs resulting in reduced immune surveillance ; ii ) mobilisation of PML causative JC virus carrying bone marrow precursor cells and splenic marginal zone B cells ; and iii ) migration of these cells to sites of inflammation such as the brain . therefore , combination of these effects is , so far , specific for the target alpha4 integrin and should not occur in general when interfering with other targets involved in leukocyte trafficking .

Identification of integrin alpha ( M ) beta ( 2 ) as an adhesion receptor on peripheral blood monocytes for … (2002 May)
identification of integrin alpha ( M ) beta ( 2 ) as an adhesion receptor on peripheral blood monocytes for cyr61 ( CCN1 ) and connective tissue growth factor ( CCN2 ) : immediate early gene products expressed in atherosclerotic lesions . cysteine rich 61 ( cyr61 , CCN1 ) and connective tissue growth factor ( CTGF , CCN2 ) are growth factor inducible immediate early gene products found in blood vessel walls and healing cutaneous wounds . We previously reported that the adhesion of endothelial cells , platelets , and fibroblasts to these extracellular matrix associated proteins is mediated through integrin receptors . In this study , we demonstrated that both cyr61 and CTGF are expressed in advanced atherosclerotic lesions of apolipoprotein E deficient mice . because monocyte adhesion and transmigration are important for atherosclerosis , wound healing , and inflammation , we examined the interaction of THP 1 monocytic cells and isolated peripheral blood monocytes with cyr61 and CTGF . THP 1 cells and monocytes adhered to cyr61 or CTGF coated wells in an activation dependent manner and this process was mediated primarily through integrin alpha ( M ) beta ( 2 ) . additionally , expression of alpha ( M ) beta ( 2 ) on human embryonic kidney 293 cells resulted in enhanced cell adhesion to cyr61 . consistent with these data , a GST fusion protein containing the I domain of the integrin alpha ( M ) subunit bound specifically to immobilized cyr61 or CTGF …

Expression of polymorphonuclear leukocyte adhesion molecules and its clinical significance in patients treated with percutaneous transluminal coronary angioplasty. (1996 Dec)
expression of polymorphonuclear leukocyte adhesion molecules and its clinical significance in patients treated with percutaneous transluminal coronary angioplasty . objectives : This study evaluated the role of neutrophil adhesion molecules LFA 1 ( cd11a / CD18 ) , Mac 1 ( cd11b / CD18 ) and p150 , 95 ( cd11c / CD18 ) in patients undergoing percutaneous transluminal coronary angioplasty ( PTCA ) . background : several recent studies have suggested that cell adhesion molecules on both neutrophils and vascular endothelial cells play an important role in the process of tissue inflammation . methods : thirty eight patients ( 30 men , 8 women ; mean / SE age 56 / 5 years , range 38 to 76 ) with single vessel coronary artery disease of the left anterior descending artery underwent coronary angioplasty . peripheral blood was sampled at baseline before , immediately after and 12 , 24 , 48 and 144 h after PTCA . The expression of CD18 , cd11a , cd11b and cd11c on the surface of polymorphonuclear leukocytes was examined by flow cytometry with monoclonal antibodies . results : In patients without subsequent restenosis , there was no change in mean channel fluorescence intensity ( MFI ) of CD18 at each sampling time . however , in the patients with restenosis , the MFI of CD18 significantly increased at 48 h after PTCA ( from 57 / 6 to 73 / 8 , p 0 . 0008 ) . The MFI of cd11b increased …

Human neutrophil adherence to thrombospondin occurs through a CD11 / CD18 independent mechanism. (1991 Jun)
human neutrophil adherence to thrombospondin occurs through a CD11 / CD18 independent mechanism . thrombospondin ( TSP ) , a 450 kDa trimeric glycoprotein secreted by platelets and endothelial cells at sites of tissue injury or inflammation , may play an important role in polymorphonuclear leukocyte ( PMN ) adherence to blood vessel walls before diapedesis . We have examined the adherence of PMN to TSP and compared it to adherence to other extracellular matrix proteins . PMN adherence to TSP coated plastic was complete by 60 min with spreading completed by 2 h . The kinetics of adhesion and spreading on TSP were similar to that of vitronectin ( VN ) , laminin ( LN ) , and fibronectin ( FN ) . activation of PMN with the calcium ionophore a23187 or the chemotactic peptide FMLP increased PMN adherence to LN and FN , but not to TSP or VN , suggesting that PMN activation may differentially regulate expression of TSP and VN receptors as compared to LN and FN receptors . The specificity of PMN adherence to TSP was confirmed by competition with saturating amounts of TSP and inhibition with anti TSP antibodies . mAb A6 . 1 , which binds to the protease resistant core of TSP , was the most effective in blocking PMN adherence to TSP . using TSP proteolytic fragments , we demonstrated that the primary interaction of PMN with TSP was mediated through the 140 kDa COOH terminal domain . inasmuch as the …

Rac regulates integrin mediated spreading and increased adhesion of T lymphocytes. (1998 Jul)
Rac regulates integrin mediated spreading and increased adhesion of T lymphocytes . leukocyte adhesion to the extracellular matrix ( ECM ) is tightly controlled and is vital for the immune response . circulating lymphocytes leave the bloodstream and adhere to ECM components at sites of inflammation and lymphoid tissues . mechanisms for regulating T lymphocyte ECM adhesion include ( i ) an alteration in the affinity of cell surface integrin receptors for their extracellular ligands and ( ii ) an alteration of events following postreceptor occupancy ( e . g . , cell spreading ) . whereas H Ras and R Ras were previously shown to affect T cell adhesion by altering the affinity state of the integrin receptors , no signaling molecule has been identified for the second mechanism . In this study , we demonstrated that expression of an activated mutant of Rac triggered dramatic spreading of T cells and their increased adhesion on immobilized fibronectin in an integrin dependent manner . This effect was not mimicked by expression of activated mutant forms of Rho , cdc42 , H Ras , or ARF6 , indicating the unique role of Rac in this event . The Rac induced spreading was accompanied by specific cytoskeletal rearrangements . Also , a clustering of integrins at sites of cell adhesion and at the peripheral edges of spread cells was observed . We demonstrate that expression of racv12 did not alter the level of expression of cell surface integrins or the affinity state …

AGEs bind to mesothelial cells via RAGE and stimulate VCAM 1 expression. (2002 Jan)
AGEs bind to mesothelial cells via RAGE and stimulate VCAM 1 expression . background : excess advanced glycation end products ( AGEs ) are formed during renal failure , and AGE formation also may be connected with the high glucose concentration of peritoneal dialysis ( PD ) fluids . To determine the effect of human peritoneal mesothelial cell ( HPMC ) exposure to glycated proteins , we studied the HPMC receptor of AGE expression ( RAGE ) , and analyzed the results of AGE RAGE interaction on adhesion molecule expression and leukocyte binding . methods : RAGE was detected by FACS analysis , and RAGE mRNA by reverse transcription polymerase chain reaction ( RT PCR ) . vascular and intercellular cell adhesion molecule ( VCAM 1 and ICAM 1 ) expression was measured by a known radiometric technique under basal conditions , after the addition of an AGE specific compound , nepsilon carboxylmethyllysine ( CML albumin ) . leukocyte adhesion on HPMC was analyzed by videomicroscopy after HPMC stimulation . results : RAGE protein was detected on HPMC , and RAGE mRNA was evidenced by RT PCR . VCAM 1 expression was stimulated by CML albumin ( P 0 . 01 ) , while ICAM 1 was unchanged . By blocking the AGE RAGE interaction , anti RAGE antibodies or recombinant RAGE inhibited the increase in VCAM 1 expression . CML albumin stimulation potentiated leukocyte adhesion to HPMC ( P 0 . 001 ) . This effect was prevented by …

Nitric oxide : an endogenous modulator of leukocyte adhesion. (1991 Jul)
nitric oxide : an endogenous modulator of leukocyte adhesion . The objective of this study was to determine whether endogenous nitric oxide ( NO ) inhibits leukocyte adhesion to vascular endothelium . This was accomplished by superfusing a cat mesenteric preparation with inhibitors of NO production , NG monomethyl L arginine ( L NMMA ) or NG nitro L arginine methyl ester ( L NAME ) , and observing single ( 30 microns diameter ) venules by intravital video microscopy . thirty minutes into the superfusion period the number of adherent and emigrated leukocytes , the erythrocyte velocity , and the venular diameter were measured ; venular blood flow and shear rate were calculated from the measured parameters . The contribution of the leukocyte adhesion glycoprotein CD11 / CD18 was determined using the CD18 specific monoclonal antibody IB4 . Both inhibitors of NO production increased leukocyte adherence more than 15 fold . leukocyte emigration was also enhanced , whereas venular shear rate was reduced by nearly half . antibody IB4 abolished the leukocyte adhesion induced by L NMMA and L NAME . incubation of isolated cat neutrophils with L NMMA , but not L NAME , resulted in direct upregulation of CD11 / CD18 as assessed by flow cytometry . decrements in venular shear rate induced by partial occlusion of the superior mesenteric artery in untreated animals revealed that only a minor component of L NAME induced leukocyte adhesion was shear rate dependent . The L NAME induced adhesion was …

VAP 1 and CD73 , endothelial cell surface enzymes in leukocyte extravasation. (2007 Dec)
VAP 1 and CD73 , endothelial cell surface enzymes in leukocyte extravasation . leukocyte extravasation from the blood into tissues is crucial for normal immune surveillance and in inflammation . traditionally molecules belonging to selectin , chemokine , integrin , and immunoglobulin super families are thought to mediate the multiple adhesive and activation events needed for a successful emigration cascade . recently , emerging evidence suggests that enzymes expressed on the surface of endothelial cells and leukocytes also contribute to the leukocyte extravasation cascade . Here we briefly review the role of vascular adhesion protein 1 ( VAP 1 ) and CD73 , 2 cell surface enzymes , in leukocyte migration form the blood into the tissues . importantly , specific enzyme inhibitors , gene deficient mice , and recombinant enzymes have recently unambiguously shown that the catalytic activity of these enzymes regulates the leukocyte traffic . The concept of enzymatic regulation of leukocyte extravasation provides new insight into the multi step adhesion cascade and opens new possibilities for inhibiting inappropriate inflammatory reaction through the use of small molecule enzyme inhibitors .