Prevention of in stent restenosis via reduction of thrombo inflammatory reactions with recombinant P selectin glycoprotein ligand 1. (2004 Jun)
prevention of in stent restenosis via reduction of thrombo inflammatory reactions with recombinant P selectin glycoprotein ligand 1 . The binding of leukocyte P selectin glycoprotein ligand 1 ( PSGL 1 ) to platelet P selectin is central to post angioplasty restenosis . although intracoronary stents limit the mechanical component of restenosis , they cause marked thrombo inflammation and neointimal proliferation leading to greater late luminal loss . We sought to demonstrate that P selectin antagonism , using recombinant PSGL 1 ( rpsgl Ig ) , is effective in reducing platelet leukocyte reactions and in stent restenosis in double injured porcine coronary arteries . Two weeks after initial injury by angioplasty to the coronary arteries , stents were implanted at the injury induced lesion site , 15 min after an i . v . bolus administration of a vehicle or rpsgl Ig ( 1 mg / kg ) . Four weeks later , adhesion of ( 51 ) Cr platelets and ( 111 ) In neutrophils and histomorphometric analyses were performed . In stent residual lumen was almost 3 fold larger in rpsgl Ig treated arteries ( 3 . 1 / 0 . 4 mm ( 2 ) ) as compared to control ( 1 . 1 / 0 . 2 mm ( 2 ) ) , which correspond to 64 vascular stenosis in control with no change in rpsgl Ig animals . For a similar injury score , in stent neointima was significantly reduced by 30 to 40 in …

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 …

Comparison of E selectin expression at mRNA and protein levels in murine models of inflammation. (2004 Mar)
comparison of E selectin expression at mRNA and protein levels in murine models of inflammation . background : Drug targeting to activated endothelial cells via E selectin is currently being explored as a new approach to treat chronic inflammatory disorders . This approach uses E selectin directed antibodies as carrier molecules to selectively deliver anti inflammatory drugs into activated endothelial cells , thereby theoretically decreasing drug associated side effects . therapeutic effects of developed drug targeting constructs will have to be tested in animal models of inflammation , in which E selectin is expressed during the course of the disease . In this study several murine models of inflammation were investigated regarding expression of E selectin . methods : E selectin expression was determined both at the mRNA level using RT PCR and at the protein level by immunohistochemistry using two monoclonal antibodies ( 10E9 . 6 and MES 1 ) . The models studied included delayed type hypersensitivity induced skin inflammation , dextran sodium sulphate induced colitis , kidney ischemia / reperfusion injury , atherosclerosis in ApoE knockout mice , and collagen induced arthritis . results : In all animal models E selectin mRNA expression was detected , although to a different extent . In contrast , only the delayed type hypersensitivity model and , to a minor extent , the collagen induced arthritis model showed E selectin protein expression . conclusion : these results stress the need to determine E selectin protein expression and not only mRNA expression …

Dynamic expression of L selectin in cell to cell interactions between neutrophils and endothelial cells in vitro. (1998 Sep)
dynamic expression of L selectin in cell to cell interactions between neutrophils and endothelial cells in vitro . neutrophil endothelial cell interactions are regulated by cell adhesion molecules and their cognate ligands . It has been proposed that L selectin and Mac 1 ( cd11b / CD18 ) , two neutrophil adhesion receptors , have sequential roles in neutrophil extravasation during inflammation . In this model , L selectin mediates rolling and initial adherence of neutrophils to endothelial cells , while Mac 1 strengthens this initial adherence and also facilitates migration of neutrophils through endothelial cells . L selectin and Mac 1 expression are known to be inversely regulated . Here an in vitro culture system has been developed to investigate in situ expression of L selectin during cell to cell interactions between neutrophils and endothelial cell monolayers by confocal immunofluorescence analysis . neutrophils underwent profound cell shape change from round to polarized cell morphology with pseudopod formation after 5 to 15 min coculture with IL 1 stimulated human endothelial cells . L selectin was redistributed to the pseudopod of the polarized neutrophils in correlation with such cellular changes . during initial cell attachment , neutrophils bound to IL 1 stimulated endothelial cells expressed a high level of L selectin in a polarized pattern . L selectin expression decreased over time during neutrophil endothelial cell interactions .

The P selectin , tissue factor , coagulation triad. (2005 Aug)
The P selectin , tissue factor , coagulation triad . The primary importance of tissue factor ( TF ) in blood coagulation and thrombus propagation has been recognized for many years . nevertheless , our view about the origin of TF activity , necessary for normal hemostasis and found in pathologic conditions , needs to be revised in the light of recent observations . pioneering work by Yale nemerson s group showed that circulating TF on microparticles ( MPs ) , could promote thrombus growth . The origin and characteristics of this blood borne TF are targets of intense research as well as intense debate . surprising observations now implicate the adhesion receptor P selectin ( P sel ) , known for its role in inflammation , in these MPs generation . P sel , translocated from granules to the cell surfaces of activated platelets and endothelial cells , was recently found to play multiple roles in hemostasis . expressed on endothelium , it can mediate platelet rolling . signaling by P sel through its receptor on leukocytes , P selectin glycoprotein ligand 1 ( PSGL 1 ) , induces the generation of TF positive , highly procoagulant MPs . In addition , P sel on activated platelets helps to recruit these MPs specifically to thrombi . In this review , we discuss the roles of P sel and TF positive MPs and highlight strategies to modulate hemostasis by modulating the P sel , TF , coagulation triad .

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 …

P selectin is upregulated early in the course of hyperoxic lung injury in mice. (1997 Feb)
P selectin is upregulated early in the course of hyperoxic lung injury in mice . while treatment with supplemental oxygen is often essential in patients with lung disease , prolonged therapy may cause lung injury by itself . although the mechanisms responsible for initiating hyperoxic lung damage almost certainly involve primary oxidative transformations , the possible contributions of inflammation to the tissue injury have been attracting increasing research activity . increases in intercellular adhesion molecule 1 ( ICAM 1 ) coincide with the inflammation , but in other models of inflammation transient adhesion mediated by members of the selectin gene family was found to be essential before ICAM 1 / beta 2 interactions could occur . We , therefore , wondered whether a similar sequence of initial transient adhesion followed by subsequent responses would be observed in hyperoxic lung inflammation . We , therefore , determined the effects of hyperoxia exposure on lung mRNA for P and E selectin in mouse lungs . We found that there was no detectable mRNA for E selectin through 72 h of hyperoxia exposure by northern blotting , but that mRNA for P selectin was detectable as early as 48 h after initiation of hyperoxia . To determine the location of P selectin upregulation we examined hyperoxia exposed mouse lungs by in situ hybridization and found that the upregulation of P selectin at 48 h was localized to large muscularized vessels , at 72 h expression was detected in some medium size muscularized vessels …

Role of P selectin in the early stage of the arthus reaction. (1997 Jan)
Role of P selectin in the early stage of the arthus reaction . P selectin is rapidly translocated to the surface of endothelial cells and platelets following exposure to chemical mediators such as histamine , thrombin and complement factors . The arthus reaction is caused by vascular injury which is initiated by the local deposition of the immune complex followed by the activation of complement and release of chemical mediators . In this report , the role of P selectin in the early stage of reverse passive arthus reaction in rat using monoclonal antibodies ( mAbs ) against rat P selectin will be investigated . intravenous administration of the mAb ARP2 4 significantly attenuated paw edema 1 h after challenging it with antigen by 31 . 5 ( 1 mg / kg ) and 44 . 7 ( 3 mg / kg ) , respectively . edema formation was also reduced by sulfatide ( 73 . 1 , 50 mg / kg ) and inositol hexakisphosphate ( insp6 ) ( 72 . 9 , 30 mg / kg ) , which have been reported to block P selectin mediated neutrophil adhesion . moreover , neutrophil accumulation into the inflammatory site in the arthus reaction was inhibited by anti P selectin mAb . P selectin expression was detected along vessel walls prior to neutrophil accumulation , as determined by immunohistochemical staining using the antibody . In addition , the expression of P selectin mRNA was induced 4 h after deposition of …

Alterations in circulating intercellular adhesion molecule 1 and L selectin : further evidence for chronic inflammation in ischemic heart disease. (1996 Sep)
alterations in circulating intercellular adhesion molecule 1 and L selectin : further evidence for chronic inflammation in ischemic heart disease . atherosclerosis is increasingly thought to be a chronic inflammatory disease . inflammation requires transmigration of leukocytes from the circulation to the tissues . adhesion of leukocytes to endothelial calls is the initial event in an inflammatory response and is mediated by expression of several adhesion molecules . In this study we characterize the contribution of intercellular adhesion molecules ( ICAM 1 ) and L selectin in patients with different coronary artery disease syndromes . serum concentrations of cicam 1 and sL selectin were measured by enzyme linked immunosorbent assay in 31 patients with stable angina , 30 patients with unstable angina , 18 patients with acute myocardial infarction and 20 healthy subjects in a control group . All patients underwent coronary angiography . Mean ( / SE ) cicam 1 levels were higher ( p 0 . 05 ) in patients with stable angina ( 249 / 6 ng / ml ) , unstable angina ( 260 / 16 ng / ml ) , or acute myocardial infarction ( 261 / 24 ng / ml ) compared with those in subjects in the control group ( 171 / 11 ng / ml ) . In contrast , levels of sL selectin were lower ( p 0 . 01 ) in patients with stable angina ( 1 . 2 / 0 . 1 microg / ml ) , unstable angina …

Soluble adhesion molecules in CSF are increased in children with severe head injury. (1999 May)
soluble adhesion molecules in CSF are increased in children with severe head injury . leukocyte endothelial adhesion molecules , critical to the development of acute inflammation , are expressed in brain as part of the acute inflammatory response to traumatic brain injury ( TBI ) . We measured the concentrations of the adhesion molecules P selectin , ICAM 1 , E selectin , L selectin , and VCAM 1 in ventricular cerebrospinal fluid ( CSF ) from children with severe TBI ( glasgow coma score 8 ) and compared these findings with those from children with bacterial meningitis . P selectin , an adhesion molecule associated with ischemia / reperfusion , was increased in children with TBI versus meningitis and control . univariate and multivariate regression analyses demonstrated associations between CSF P selectin and child abuse and age of 4 years , and a significant , independent association between CSF intercellular adhesion molecule 1 ( ICAM 1 ) and child abuse . these results are consistent with a specific acute inflammatory component to TBI in children . future studies of secondary injury mechanisms and therapy after TBI should assess on the roles of P selectin and ICAM 1 in injury and repair processes in brain after TBI .

TACI ligand interactions are required for T cell activation and collagen induced arthritis in mice. (2001 Jun)
TACI ligand interactions are required for T cell activation and collagen induced arthritis in mice . interactions of the tumor necrosis factor superfamily members B lymphocyte stimulator ( BLyS ) and a proliferation inducing ligand ( april ) with their receptors transmembrane activator and CAML interactor ( TACI ) and B cell maturation molecule ( BCMA ) on B cells play an important role in the humoral immune response . whereas BCMA is restricted to B cells , TACI is also expressed on activated T cells ; we show here that TACI Fc blocks the activation of T cells in vitro and inhibits antigen specific T cell activation and priming in vivo . In a mouse model for rheumatoid arthritis ( RA ) , an autoimmune disease that involves both B and T cell components , TACI Fc treatment substantially inhibited inflammation , bone and cartilage destruction and disease development . Thus , BLyS and / or april are important not only for B cell function but for T cell mediated immune responses . inhibition of these ligands might have therapeutic benefits for autoimmune diseases , such as RA , that involve both B and T cells .

Structural requirements regulate endoproteolytic release of the L selectin ( cd62l ) adhesion receptor from the cell surface of leukocytes. (1995 Sep)
structural requirements regulate endoproteolytic release of the L selectin ( cd62l ) adhesion receptor from the cell surface of leukocytes . L selectin mediates leukocyte rolling on vascular endothelium at sites of inflammation and lymphocyte migration to peripheral lymph nodes . L selectin is rapidly shed from the cell surface after leukocyte activation by a proteolytic mechanism that cleaves the receptor in a membrane proximal extracellular region . This process may allow rapid leukocyte detachment from the endothelial surface before entry into tissues . In this study , the structural requirements for regulation of human L selectin endoproteolytic release were examined through analysis of chimeric selectin molecules and mutant L selectin receptors . The use of chimeric selectins and a cytoplasmic tail truncation mutant demonstrated that the extracellular membrane proximal 15 amino acid region of L selectin is required for endoproteolytic release . The introduction of alanine scanning mutations within this membrane proximal region did not prevent endoproteolytic release , indicating that a specific amino acid motif was not an absolute requirement for cleavage . furthermore , alterations within the putative primary cleavage site ( K283 S284 ) resulted in either constitutive endoproteolytic release of the receptor or inhibition of cell activation induced shedding to variable extents . The length of the membrane proximal region was also critical since truncations of this region completely abolished endoproteolytic release . Thus , release of L selectin is likely to be regulated by the generation of an appropriate tertiary conformation within the membrane …

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 . …

Effect of CP 96 , 345 on the expression of adhesion molecules in acute pancreatitis in mice. (2007 May)
effect of CP 96 , 345 on the expression of adhesion molecules in acute pancreatitis in mice . We investigated the effect of a specific neurokinin 1 receptor ( NK1R ) antagonist , CP 96 , 345 , on the regulation of the expression of adhesion molecules ICAM 1 , VCAM 1 , E selectin , and P selectin as well as leukocyte recruitment during acute pancreatitis ( AP ) . AP was induced in male Balb / C mice by 10 consecutive hourly intraperitoneal injections of caerulein . In the treatment groups , CP 96 , 345 was administered at 2 . 5 mg / kg ip either 30 min before or 1 h after the first caerulein injection . animals were killed , and the lungs and pancreas were isolated for RNA extraction and RT PCR or for immunohistochemical staining . mRNA expression of the four adhesion molecules was upregulated in the pancreas during AP . treatment with CP 96 , 345 effectively reduced the mRNA expression of P selectin and E selectin but not ICAM 1 and VCAM 1 . In the lung , ICAM 1 , E selectin , and P selectin mRNA expression increased during AP . antagonist treatment suppressed this elevation . similar expression patterns were seen in the immunohistochemical stainings . intravital microscopy of the pancreatic microcirculation revealed the effect of CP 96 , 345 on leukocyte recruitment . The present study provides important information on the relationship between NK1R activation and the …

Soluble P selectin antagonist mediates rolling velocity and adhesion of leukocytes in acutely inflamed venules. (2001 Apr)
soluble P selectin antagonist mediates rolling velocity and adhesion of leukocytes in acutely inflamed venules . objective : leukocyte rolling is recognized as an important event in facilitating the extravasation of leukocytes from the vascular to the interstitial compartment , and is mediated by the selectin family of cell adhesion molecules . The aim of this study was to evaluate and characterize the rolling behavior of leukocytes in a model of acute inflammation using a novel soluble selectin ligand directed against P selectin . methods : feline mesenteric postcapillary venules were visualized using intravital microscopy prior to and following exposure to leukotriene C4 ( LTC4 ) in animals pretreated with vehicle ( saline ) and the P selectin antagonist rpsgl Ig . results : A concentration of 500 pM LTC4 induced a threefold and sixfold elevation in leukocyte rolling flux and adhesion , respectively , compared to baseline values ( p 0 . 05 ) . administration of rpsgl Ig had no effect on LTC4 induced leukocyte rolling flux but significantly attenuated the increase in the fraction of rolling leukocytes ( p 0 . 05 ) . In addition , rpsgl Ig inhibited the LTC4 induced reductions in leukocyte rolling velocity ( p 0 . 001 ) . finally , LTC4 induced leukocyte adhesion in animals pretreated with rpsgl Ig was reduced by 60 , compared to vehicle treated animals ( p 0 . 05 ) . conclusions : LTC4 induces leukocyte rolling and adhesion in feline mesenteric venules in …

Lysosomal targeting of P selectin is mediated by a novel sequence within its cytoplasmic tail. (1998 Feb)
lysosomal targeting of P selectin is mediated by a novel sequence within its cytoplasmic tail . signals controlling the intracellular targeting of many membrane proteins are present as short sequences within their cytoplasmic domains . P selectin is a type I membrane protein receptor for leukocytes , acting during the inflammation response . heterologous expression experiments have demonstrated that its 35 residue cytoplasmic tail contains signals for targeting to synaptic like microvesicles , dense cored granules , and lysosomes . We have examined the lysosomal targeting information present within the cytoplasmic tail by site directed mutagenesis of horseradish peroxidase P selectin chimeras followed by transient transfection in H . Ep . 2 cells . assaying lysosomal targeting by subcellular fractionation as well as intracellular proteolysis , we have discovered a novel lysosomal targeting signal , KCPL , located within the C1 domain of the cytoplasmic tail . alanine substitution of this tetrapeptide reduced lysosomal targeting to the level of a tailless horseradish peroxidase P selectin chimera , which was previously found to be deficient in both internalization and delivery to lysosomes . A proline residue within this lysosomal targeting signal makes a major contribution to the efficiency of lysosomal targeting . A diaminobenzidine density shift procedure established that chimeras with an inactivated KCPL sequence are present within transferrin positive compartments . Such a mutant also displays an increased level of expression at the plasma membrane . Our results indicate that the sequence KCPL within the cytoplasmic tail of P selectin …

Role of P selectin cytoplasmic domain in granular targeting in vivo and in early inflammatory responses. (1998 Dec)
Role of P selectin cytoplasmic domain in granular targeting in vivo and in early inflammatory responses . P selectin is an adhesion receptor for leukocytes expressed on activated platelets and endothelial cells . The cytoplasmic domain of P selectin was shown in vitro to contain signals required for both the sorting of this protein into storage granules and its internalization from the plasma membrane . To evaluate in vivo the role of the regulated secretion of P selectin , we have generated a mouse that expresses P selectin lacking the cytoplasmic domain ( deltact mice ) . The deletion did not affect the sorting of P selectin into alpha granules of platelets but severely compromised the storage of P selectin in endothelial cells . unstored P selectin was proteolytically shed from the plasma membrane , resulting in increased levels of soluble P selectin in the plasma . The deltact P selectin appeared capable of mediating cell adhesion as it supported leukocyte rolling in the mutant mice . however , a secretagogue failed to upregulate leukocyte rolling in the deltact mice , indicating an absence of a releasable storage pool of P selectin in the endothelium . furthermore , the neutrophil influx into the inflamed peritoneum was only 30 of the wild type level 2 h after stimulation . Our results suggest that different sorting mechanisms for P selectin are used in platelets and endothelial cells and that the storage pool of P selectin in endothelial cells is functionally important during …

Molecular determinants of the prothrombogenic phenotype assumed by inflamed colonic venules. (2005 Apr)
molecular determinants of the prothrombogenic phenotype assumed by inflamed colonic venules . although platelets have been implicated in the pathogenesis of human inflammatory bowel diseases , little is known about the magnitude of platelet accumulation in the inflamed bowel , what regulates this process , and its relevance to the overall inflammatory response . In this study , intravital video microscopy was used to monitor the trafficking of platelets and leukocytes and vascular permeability in colonic venules during the development of colonic inflammation induced by 3 dextran sodium sulfate ( DSS ) . blocking antibodies directed against different adhesion molecules as well as P selectin deficient mice were used to define the adhesive determinants of DSS induced platelet recruitment . DSS induced an accumulation of adherent platelets that was temporally correlated with the appearance of adherent leukocytes and with disease severity . platelet adhesion and , to a lesser extent , leukocyte adhesion were attenuated by immunoblockade of P selectin and its ligand P selectin glycoprotein ligand 1 ( PSGL 1 ) , with contributions from both platelet and endothelial cell associated P selectin . DSS induced a rapid and sustained increase in vascular permeability that was greatly attenuated in P selectin deficient mice . P selectin bone marrow chimeras revealed that both endothelial cell and platelet associated P selectin contribute to the P selectin expression detected in the inflamed colonic microvasculature , with endothelial P selectin making a larger contribution . Our findings indicate that colonic inflammation is associated …

Blocking both E selectin and P selectin inhibits endotoxin induced leukocyte infiltration into the eye. (1997 Apr)
blocking both E selectin and P selectin inhibits endotoxin induced leukocyte infiltration into the eye . The initial contact between leukocytes and the vascular endothelium at sites of inflammation is mediated by selectins . The purpose of this study was to investigate the role of the two selectins expressed on the vascular endothelium , E selectin and P selectin , in the pathogenesis of endotoxin induced uveitis . endotoxin induced uveitis was produced in female C3H / HeN mice using salmonella typhimurium endotoxin injected into one hind footpad . At the time of endotoxin injection mice were treated with an intraperitoneal injection of a monoclonal antibody against E selectin or P selectin , a combination of both anti selectin antibodies , or isotype matched control antibodies . In a second set of experiments , antibody treatment was administered 6 hr after endotoxin injection , when inflammatory cells are already entering the eye . ocular inflammation was graded histologically by a masked observer . When administered at the time of endotoxin injection , anti P selectin antibody decreased ocular inflammation by 37 compared to control animals ( P 0 . 05 ) . there was no statistical decrease in ocular inflammation in animals treated with anti E selectin antibody . The combination of anti P selectin and anti E selectin antibodies decreased infiltrating inflammatory cells by 61 ( P 0 . 01 ) . When treatment was delayed until 6 hr after endotoxin injection , the combination of anti P selectin …

Lymphocyte recruitment and the kinetics of adhesion receptor expression during the pulmonary immune response to particulate antigen. (1998 Jan)
lymphocyte recruitment and the kinetics of adhesion receptor expression during the pulmonary immune response to particulate antigen . The selectins and beta2 integrins participate in the recruitment of neutrophils in acute pulmonary inflammation . however , the cell adhesion receptors that mediate lymphocyte trafficking into the lung have not been defined . This study examined the relationship between cell adhesion molecules on the pulmonary vasculature and on lymphocytes recovered from the lung during a pulmonary immune response to intratracheal ( I . T . ) sheep red blood cells ( srbcs ) in sensitized c57bl / 6J mice . silver enhanced immunogold staining and reverse transcriptase polymerase chain reaction of lung tissues revealed sustained induction of VCAM 1 , E selectin , and P selectin on the pulmonary vasculature for up to 7 days after I . T . SRBC challenge . neither the MECA 79 nor MECA 367 antigens were induced on the pulmonary vasculature during this period . In the peripheral blood , both CD4 and CD8 T cell subsets showed an initial increase in P selectin ligand expression after I . T . SRBC challenge . The number of P selectin ligand positive T cells in the peripheral blood fell as T cells with both P selectin and , to a lesser extent , E selectin ligands accumulated in the bronchoalveolar lavage fluid . We conclude that I . T . SRBC challenge in sensitized mice elicits prolonged synthesis of P selectin , E selectin , and …