UMLS:C0001511 - FACTA Search

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Query: UMLS:C0001511 (Adhesion)
5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adhesion molecules and chemoattractants are thought to play a critical role in the homing of leukocytes to sites of vascular lesions. Apo-E deficiency in mice creates an atherosclerotic model that mimics vascular lesions in man. Little is known on the effect of Apo-E deficiency on expression of adhesion molecules in the hearts of these animals. In this study, male C57BL6 and Apo-E deficient mice were fed a chow diet over periods of time (0 to 20 weeks). The transcription levels of major adhesion molecules (ICAM-1, PECAM-1), present in the heart, were followed by northern blots. Immunohistochemistry was used to localize these adhesion molecules in the heart. Results show a significant increase in gene transcription levels of ICAM-1 and PECAM-1 in Apo-E animals, but not wild type, at 16 and 20 weeks of chow diet. Such increase in levels of transcription was not observed in younger Apo-E and C57BL6 animals (0, 6 weeks of diet). ICAM-1 and PECAM-1 were strongly expressed in the endocardium and heart microvessels. In contrast, VCAM-1 was poorly stained, with only an occasional expression on the endocardium and arterioles. Enhanced gene expression levels of heart ICAM-1 and PECAM-1 observed in Apo-E deficient mice, but not in control animals, appears to induce the initial stages of an inflammatory reaction. Such observations, not previously reported, may induce heart vascular remodeling.
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PMID:Increased ICAM-1 and PECAM-1 transcription levels in the heart of Apo-E deficient mice in comparison to wild type (C57BL6). 1137 87

Platelet/Endothelial Cell Adhesion Molecule-1 (PECAM-1 or CD31) is thought to be a vascular-specific protein, but its function has not been clearly defined. Here, we demonstrate by using confocal immunofluorescence microscopy that PECAM-1 is first detected in the mouse blastocyst, which contains no vascular cells, and its expression is restricted to the pluripotent inner cell mass (ICM) cells. Expression is localized to cell-cell borders of the ICM and is detected at the very first signs of blastocoel formation. Consistent with these observations is that embryonic transcripts of PECAM-1 mRNA, as detected by RT-PCR, greatly increase during the morula-to-blastocyst transition and seven of the eight known alternatively spliced isoforms of PECAM-1 are expressed in the blastocyst. The synthesis of PECAM-1 is independent of compaction, cytokinesis, and DNA replication, as it is detected in embryos that are chronologically at the blastocyst stage following culture of 8-cell embryos in Ca2+-free medium, or medium containing cytochalasin D or aphidicolin, respectively. By the late blastocyst stage, PECAM-1 expression is restricted to the pluripotent epiblast, at which point it has a mutually exclusive expression pattern to that of type IV collagen, a basement membrane marker. The reduction in PECAM-1 transcripts in retinoic acid-induced differentiation of F9 teratocarcinoma cells, a model of epiblast-to-primitive endoderm differentiation, confirmed the epiblast-specific expression of PECAM-1. By the egg cylinder stage of development, at which point the epiblast is no longer pluripotent, PECAM-1 is not detected. This ICM-specific pattern of expression suggests a novel developmental role of PECAM-1 that is independent of its function in vascular ontogeny.
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PMID:Inner cell mass-specific expression of a cell adhesion molecule (PECAM-1/CD31) in the mouse blastocyst. 1139 2

Adhesion molecules on endothelial cells are known to be important ligands for malaria infected red blood cells (PRBC) [Mol Biochem Parasitol, 76, (1996) 1], and may be involved in the pathogenic process of cerebral malaria (CM) which is the most serious complication of falciparum malaria, through enhancing micro embolism or sequestration in the capillaries of the brain. PECAM-1/CD31 is one of these candidate ligands and is coded by a polymorphic gene. Two hundred and ten Thai malaria patients (43 cerebral, 89 severe and 78 uncomplicated) were analyzed for their genetic polymorphism of CD31 to examine the clinical relationship between the disease and specific genotypes. Four alleles were defined 125 valine (V)-563 asparagine (N); 125V-563 serine (S); 125 leucine (L)-563N; and 125L-563S. We found that the frequency of the 125 V/V 563 N/N genotype was significantly high in CM patients as compared with severe cases without CM (P<0.01, OR=2.92), suggesting that this genotype is one of the risk factors for CM.
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PMID:Association of adhesion molecule PECAM-1/CD31 polymorphism with susceptibility to cerebral malaria in Thais. 1171 9

We and others have recently defined that Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1/CD31) functions as a negative regulator of platelet-collagen interactions involving the glycoprotein VI/Fc receptor gamma chain (GPVI/FcR-gamma chain) signaling pathway.1,2 In this study, we hypothesized that PECAM-1 may be physically and functionally associated with Fc gamma RIIa on the platelet membrane. The functional relationship between PECAM-1 and Fc gamma RIIa was assessed by determining the effect of anti-PECAM-1 monoclonal antibody Fab fragments on Fc gamma RIIa-mediated platelet aggregation and heparin-induced thrombocytopenia (HITS)-mediated platelet aggregation. Preincubation of washed platelets with monoclonal antibody fragments of 2BD4 directed against PECAM-1 and IV.3 directed against Fc gamma RIIa completely blocked Fc gamma RIIa-mediated platelet aggregation and HITS-mediated platelet aggregation, whereas anti-CD151 antibody had no blocking effect. Coengagement of Fc gamma RIIa and PECAM-1 resulted in negative regulation of Fc gamma RIIa-mediated phospholipase C gamma 2 activation, calcium mobilization, and phosphoinositide 3-kinase-dependent signaling pathways. In addition, the physical proximity of Fc gamma RIIa and PECAM-1 was confirmed by using fluorescence resonance energy transfer and coimmunoprecipitation studies. These results indicate that PECAM-1 and Fc gamma RIIa are colocalized on the platelet membrane and PECAM-1 down-regulates Fc gamma RIIa-mediated platelet responses.
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PMID:Physical proximity and functional interplay of PECAM-1 with the Fc receptor Fc gamma RIIa on the platelet plasma membrane. 1289 67

The objective of this study was to determine whether absence of endothelial nitric oxide synthase (eNOS) affects the expression of cell surface adhesion molecules in endothelial cells. Murine lung endothelial cells (MLECs) were prepared by immunomagnetic bead selection from wild-type and eNOS knockout mice. Wild-type cells expressed eNOS, but eNOS knockout cells did not. Expression of neuronal NOS and inducible NOS was not detectable in cells of either genotype. Upon stimulation, confluent wild-type MLECs produced significant amounts of NO compared with N(omega)-monomethyl-l-arginine-treated wild-type cells. eNOS knockout and wild-type cells showed no difference in the expression of E-selectin, P-selectin, intracellular adhesion molecule-1, and vascular cell adhesion molecule-1 as measured by flow cytometry on the surface of platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31)-positive cells. Both eNOS knockout and wild-type cells displayed the characteristics of resting endothelium. Adhesion studies in a parallel plate laminar flow chamber showed no difference in leukocyte-endothelial cell interactions between the two genotypes. Cytokine treatment induced endothelial cell adhesion molecule expression and increased leukocyte-endothelial cell interactions in both genotypes. We conclude that in resting murine endothelial cells, absence of endothelial production of NO by itself does not initiate endothelial cell activation or promote leukocyte-endothelial cell interactions. We propose that eNOS derived NO does not chronically suppress endothelial cell activation in an autocrine fashion but serves to counterbalance signals that mediate activation.
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PMID:Role of endothelial nitric oxide synthase in endothelial activation: insights from eNOS knockout endothelial cells. 1507 19

Adhesion of circulating cells to the arterial surface is among the first detectable events in atherogenesis. Cellular adhesion molecules, expressed by the vascular endothelium and by circulating leucocytes, mediate cell recruitment and their transendothelial migration. Platelet endothelial cellular adhesion molecule 1 (PECAM-1/CD31), involved in this migration, has been associated with the developmental course of atherosclerosis. A few studies have investigated an association between coronary heart disease and single nucleotide polymorphisms (SNPs) located in functionally important domains of the PECAM-1/CD31 gene. In particular, Ser563Asn and Gly670Arg SNPs have been described as susceptibility factors involved in acute myocardial infarction (AMI) in the Japanese male population. To confirm these observations, we studied 96 male patients (mean age 40 years; age range 20-46) affected by AMI and 118 healthy male controls (mean age 38 years, age range: 20-55), and analysed for the following PECAM-1/CD31 SNPs: Val125Leu, Asn563Ser and Gly670Arg. The frequency of the Gly670Arg polymorphism was significantly higher in patients with AMI (58.9% vs. 48.3%; P = 0.019), whereas the frequencies of the other two SNPs (Leu125Val and Ser563Asn) were not significantly different between patients and controls. By comparing the observed number of 670Arg/Arg genotypes in the patients with the expected number, calculated from the allele frequency in a healthy population, a significance of P = 0.02 (odds ratio, 2.04; 95% CI: 1.1-3.7) was obtained, supporting a recessive model of inheritance. Hence, the differences between patients and controls are significant, but relatively small. However, as AMI is a multifactorial disease, any single mutation will only provide a small or modest contribution to the risk, which also depends on environmental interaction. All in all, we believe that the results of the present study would add support to the role of pro/anti-inflammatory genotypes in determining susceptibility or resistance to immune-inflammatory diseases, including atherosclerosis.
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PMID:Association between platelet endothelial cellular adhesion molecule 1 (PECAM-1/CD31) polymorphisms and acute myocardial infarction: a study in patients from Sicily. 1526 22

In the present article we will focus on the adhesion molecules expressed by mouse primordial germ cells (PGCs) and will discuss the role that they play, or are believed to play, in two crucial processes of PGC development, namely cell lineage specification and migration into the gonadal ridges. Recent findings indicate that the adhesion-dependent allocation of the PGC precursors to a niche within the epiblast and the forming extraembryonic mesoderm during the pre-gastrulation period is crucial for their commitment. Subsequently, PGC migration and homing within the gonadal ridges require integrated signals involving contact of PGCs with extracellular matrix molecules and cellular substrates or repulsion from them, adhesion among PGCs themselves and attraction by the developing gonads. A number of adhesion, or putative adhesion molecules, have been identified in mammalian PGCs, mainly in the mouse. These molecules belong to three adhesion molecule families such as cadherins (E-P- and N-cadherins), integrins and the IgG superfamily (PECAM-1). Moreover oligosaccarides (LewisX) and growth factor receptors (c-Kit) can also play adhesive roles in some stages of PGC development. An understanding of how genes encoding adhesive molecules are regulated in PGCs and the molecular pathways associated with the functions of adhesion receptors is crucial in furthering our knowledge of PGC biology. Adhesion molecules might once again turn out to be crucial in controlling not only the germ cell lineage and PGC migration but also the PGC differentiation fate itself.
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PMID:Adhesion molecules for mouse primordial germ cells. 1557 91

Endothelial cell junctional adhesion molecule (JAM)-C has been proposed to regulate neutrophil migration. In the current study, we used function-blocking mAbs against human JAM-C to determine its role in human leukocyte adhesion and transendothelial cell migration under flow conditions. JAM-C surface expression in HUVEC was uniformly low, and treatment with inflammatory cytokines TNF-alpha, IL-1beta, or LPS did not increase its surface expression as assessed by FACS analysis. By immunofluorescence microscopy, JAM-C staining showed sparse localization to cell-cell junctions on resting or cytokine-activated HUVEC. Surprisingly, staining of detergent-permeabilized HUVEC revealed a large intracellular pool of JAM-C that showed little colocalization with von Willebrand factor. Adhesion studies in an in vitro flow model showed that functional blocking JAM-C mAb alone had no inhibitory effect on polymorphonuclear leukocyte (PMN) adhesion or transmigration, whereas mAb to ICAM-1 significantly reduced transmigration. Interestingly, JAM-C-blocking mAbs synergized with a combination of PECAM-1, ICAM-1, and CD99-blocking mAbs to inhibit PMN transmigration. Overexpression of JAM-C by infection with a lentivirus JAM-C GFP fusion protein did not increase adhesion or extent of transmigration of PMN or evoke a role for JAM-C in transendothelial migration. These data suggest that JAM-C has a minimal role, if any, in PMN transmigration in this model and that ICAM-1 is the preferred endothelial-expressed ligand for PMN beta(2) integrins during transendothelial migration.
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PMID:Neutrophil transmigration under shear flow conditions in vitro is junctional adhesion molecule-C independent. 1744 72

Inflammation has recently proven to be associated with the pathogenesis of atherosclerosis and inflammatory genes are good candidates for the risk of developing atherosclerosis. The early phase of atherosclerosis involves the recruitment of inflammatory cells from the circulation and their transendothelial migration. This process is mainly mediated by cellular adhesion molecules, which are expressed by the vascular endothelium and by circulating leukocytes in response to several inflammatory stimuli. Adhesion of circulating cells to the arterial surface is among the first detectable events in atherogenesis. Cellular adhesion molecules, expressed by the vascular endothelium and by circulating leukocytes, mediate cell recruitment and their transendothelial migration. Platelet endothelial cellular adhesion molecule-1 (PECAM-1/CD31), involved in this migration, has been associated with the developmental course of atherosclerosis. Studies have investigated an association between coronary heart disease (CHD) and single nucleotide polymorphisms (SNP) located in functionally important domains of the PECAM-1/CD31 gene, with contrasting results. In particular, we previously analyzed for the following PECAM-1/CD31 SNP: Val125Leu, Asn563Ser, and Gly670Arg. The frequency of the Gly670Arg polymorphism was significantly higher in patients with myocardial infarction (MI), whereas the frequencies of the other two SNP (Leu125Val and Ser563Asn) were not significantly different between patients and controls. To check the validity of our results, we have analyzed the distribution of these SNP in centenarian men (age >99) from our homogeneous Sicilian population, since our previous studies have demonstrated that alleles associated with MI susceptibility are not included in the genetic background favoring longevity. We showed, as regard to polymorphisms of PECAM-1/CD31, that there were no significant differences between male patients affected by MI, male controls, and male centenarians. According to our hypothesis present results seemingly do not support a role for these SNP in conferring the susceptibility to MI at least in this Italian population.
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PMID:PECAM-1/CD31 in infarction and longevity. 1746 Jan 71

Exposure to airborne particles has been associated with an increase in cardiopulmonary events. Endothelial cells could be playing an important role in the response to airborne particles due their involvement in proinflammatory events, and there is some evidence of particle translocation from lung into circulation. One of the initiating events of inflammation is endothelial activation. We determined the concentration-response effect of a particulate matter with different aerodynamic sizes (PM2.5 [particulate matter with aerodynamic diameter of 2.5 microm and less] and PM10 [particulate matter with aerodynamic diameter of 10 microm and less]) obtained from Mexico City on human umbilical vein endothelial cells (HUVEC). The adhesion of monocytic U937 cells to HUVEC and the expression of early (E- and P-selectins) and late (ICAM-1, PECAM-1, VCAM-1) adhesion molecules were tested. Adhesion of U937 cells to HUVEC was evaluated by coculture experiments using [3H]thymidine-labeled U937 cells and the expression of adhesion molecules was evaluated by flow cytometry. Tumor necrosis factor (TNF)-alpha was used as a positive control of endothelial activation. Our results showed that both PM2.5 and PM10 induced the adhesion of U937 cells to HUVEC, and their maximal effect was observed at 20 microg/cm2. This adhesion was associated with an increase in the expression of all adhesion molecules evaluated for PM10, and E-selectin, P-selectin, and ICAM-1 for PM2.5. In general, maximum expression of adhesion molecules induced by PM2.5 and PM10 was obtained with 20 microg/cm2; however, PM10-induced expression was observed from 5 microg/cm2. E-selectin and ICAM-1 had the strongest expression in response to particles. In conclusion, PM2.5 and PM10 induce the activation of HUVEC, leading to monocytic adhesion via the expression of adhesion molecules, suggesting that these particles may participate in the development of inflammatory diseases. The role of these events in the development of diseases such as atherosclerosis is likely to be evaluated.
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PMID:PM2.5 and PM10 induce the expression of adhesion molecules and the adhesion of monocytic cells to human umbilical vein endothelial cells. 1788 56

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