Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to analyze the onset mechanism of experimental autoimmune uveoretinitis (EAU), two experimental models were used; one was EAU induced by one injection of purified bovine interphotoreceptor retinoid-binding protein (IRBP) with complete Freund's adjuvant in Lewis rat, and the other was an IRBP-induced autoimmune uveoretinitis that occurred spontaneously in nude (nu/nu) mice at 4 weeks of age reconstituted by the grafting of rat embryonic thymus (TG nude mouse). EAU develops when the IRBP-reactive lymphocytes in the regional lymph-nodes are activated. Activation begins when the T lymphocyte recognizes the peptide for the epitope bound to a major histocompatibility complex (MHC) molecule in the antigen-presenting cell by way of the T-cell receptor (TCR). In EAU, ten peptide residues p1182-1191 of the IRBP amino acid sequence, were revealed to be sufficiently capable of lymphocyte activation for EAU, and it was also shown that amino acid positions 1182W (tryptophane), 1185G (glycine), 1186V (valine) and 1188P (proline) of IRBP play important roles as the epitopes or agretopes in developing EAU. On the other hand, two amino acids of IRBP, amino acid positions 1182W (tryptophane) and 1194P (proline) were shown to be the agretopes inducing autoimmune uveoretinitis in the TG nude mouse. A study of the variable region of the TCR with a residual p1182-1194 specific T-cell line from the TG nude mouse revealed that as many as 96% utilized the T-cell receptor V beta 6 gene and that the peptide-MHC molecule complex was recognized by restricted receptors. Adhesion molecules such as ICAM-1 and LFA-1 were also found to play an important role as cofactors in activation of lymphocytes in the antigen-recognition process of EAU. Uveoretinitis seemed to result from an immune reaction in the eye occurring when the T lymphocyte arrives there, activating the immunological process. ICAM-1 and LFA-1 were also found to be involved in the infiltration process of inflammatory cells: our immunohistological examination revealed that ICAM-1 was present in the retinal pigment epithelium and epithelium of the ciliary body composing the blood-ocular barrier. In contrast, LFA-1 was expressed in the infiltrating cells. Finally, the tolerance of IRBP was discussed and it was experimentally demonstrated that the absence of IRBP-induced uveoretinitis in human beings and certain experimental animals resulted from endogenous IRBP serving as a tolerogen; we assumed that the breakdown of this self-tolerance would induce EAU due to thymic dysfunction or IRBP antigen injection.
 ...
PMID:[The onset mechanism of experimental autoimmune uveoretinitis induced by interphotoreceptor retinoid-binding protein]. 128 51

The alternatively spliced type III connecting segment (IIICS) region of fibronectin contains two distinct sites that support the adhesion of melanoma cells. These sites are contained within the synthetic peptides CS1 and CS5 (residues 1-25 and 90-109 of the IIICS, respectively). Recently, the cellular receptor for the CS1 site has been identified as the integrin heterodimer alpha 4 beta 1. In this report, we have investigated the role of the CS5 sequence in melanoma cell adhesion and the identity of its receptor. Adhesion to CS5, when presented to cells as an immobilized IgG conjugate, was blocked by antifunctional monoclonal antibodies directed against either the alpha 4 or beta 1 integrin subunits, but not by antibodies against other subunits, implying that alpha 4 beta 1 is also the receptor for CS5. In peptide inhibition experiments, CS5 was inhibitory for melanoma cell spreading on both CS5-IgG and CS1-IgG conjugates; conversely, CS1 inhibited spreading on both CS1-IgG and CS5-IgG. In both cases, peptide inhibition could be outcompeted by increasing the concentration of substrate-bound conjugate. These results suggest that CS1 and CS5 are recognized by the same or overlapping sites on alpha 4 beta 1. The minimal active sequence within CS5, the tetrapeptide Arg-Glu-Asp-Val (REDV), is somewhat related to the Arg-Gly-Asp-Ser (RGDS) sequence that represents a major active site in the central cell-binding domain (CCBD) of fibronectin. When RGDS peptide homologues were tested for their ability to inhibit spreading of melanoma cells on CS1- and CS5-IgG conjugates, GRGDS, GRGES, and REDV were found to be inhibitory, while GRDGS had no effect. In contrast, spreading on a fibronectin fragment containing the CCBD was inhibited by GRGDS only. GRGDS was also able to elute alpha 4 beta 1 specifically from a CS1 affinity column, confirming directly that alpha 4 beta 1-IIICS interactions are sensitive to peptides containing this recognition motif. Because the minimal active sequence within CS1 is the tripeptide Leu-Asp-Val (LDV; Komoriya et al., manuscript submitted for publication), these findings together define a new adhesive recognition sequence, X-Asp-Y, used by alpha 4 beta 1 for binding to fibronectin. The central aspartate residue in this tripeptide is almost always essential, but some flexibility in the amino acid residues at X (glycine, leucine, or glutamic acid) and Y (serine or valine) is tolerated. Potential models for the interaction of the IIICS region with alpha 4 beta 1 are discussed.
 ...
PMID:The CS5 peptide is a second site in the IIICS region of fibronectin recognized by the integrin alpha 4 beta 1. Inhibition of alpha 4 beta 1 function by RGD peptide homologues. 175 Sep 29

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.
 ...
PMID:Association of adhesion molecule PECAM-1/CD31 polymorphism with susceptibility to cerebral malaria in Thais. 1171 9