Screening expressed sequence tag databases for endothelial-specific homologs to human junctional adhesion molecule (JAM) and A33-Ag, we identified a protein of 298 aa that represents the recently described vascular endothelial-JAM (VE-JAM)/JAM 2. We confirmed VE-JAM/JAM 2 expression to be restricted to the high endothelial venule of tonsil and lymph nodes, and we further expanded the localization to the endothelium of arterioles in and around inflammatory and tumor foci. In our functional characterizations of VE-JAM/JAM 2, we discovered that it can function as an adhesive ligand for the T cell line J45 and can interact with GM-CSF/IL-4-derived peripheral blood dendritic cells, circulating CD56+ NK cells, circulating CD56+CD3+ NK/T cells, and circulating CD56+CD3+CD8+ cytolytic T cells. In the course of our studies, we also isolated and characterized the functional VE-JAM/JAM 2 receptor, which, upon cloning, turned out to be a submitted sequence representing JAM 3 (accession number NP 113658). With these understandings, we have characterized a protein-interacting pair that can be important in the role of T, NK, and dendritic cell trafficking and inflammation.
Cell-cell interactions of the mucosal epithelia are important for the maintenance and establishment of epithelial barrier function. During events of inflammation, such cell-cell interactions are often disrupted, resulting in a leaky epithelial barrier, which in turn can lead to various inflammatory and infective dysfunctions. Human junctional adhesion molecule (huJAM), found on the mucosal epithelia and vascular endothelia of many major organ systems, is a membrane glycoprotein which resolves to a doublet band of approximately 40 and approximately 37 kDa under SDS-PAGE analysis, representing differentially glycosylated forms of the same protein. huJAM was localized to the lateral membrane of Caco-2 cells (a human colonic epithelial cell line) monolayers, in an area basolateral of the epithelial tight junctions (TJ). Through functional and biochemical assays, we show huJAM to be able to homotypically associate and to participate in TJ restitution after trypsin-EDTA disruption. Furthermore, we also observed a migration of huJAM expression toward areas of cell-cell contacts during events of cell adhesion and monolayer formation. These qualities makes huJAM a likely player in the regulation of cell-cell contacts and the subsequent formation of TJs.
MAdCAM-1 expression may be important in the recruitment of lymphocytes to the liver during inflammation.
Using monoclonal antibodies to cell surface antigens, we studied lymphocyte subsets in 15 patients with primary Sjögren's syndrome. The absolute number of OKT8‐positive cells (reactive with T suppressor/cytotoxic cells) was significantly decreased in such patients (353 ± 186/mm3) compared to age‐matched controls (631 ± 150/mm3) (P<0.001). The number of OKT4‐positive cells (reactive with T helper/inducer cells) was comparable in both groups (932 ± 588/mm3 versus 1.073 ± 290/mm3). The ratio of OKT4/OKT8‐reactive peripheral blood lymphocytes was increased (>2.4) in 67% of these patients and ranged from 1.0 to 6.4 (normal = 1.8 ± 0.3). OKT4‐positive cells were the predominant subset in lip biopsy specimens stained with immunofluorescence or immunoperoxidase techniques; the OKT4/OKT8 ratio exceeded 3.0 in all 5 patients examined. In 1 patient with pseudolymphoma, a lymph node biopsy specimen contained 80% T cells with an OKT4/OKT8 ratio of 3.2. Thus, OKT4‐positive cells predominated in the peripheral blood lymphocytes as well as in sites of inflammation in primary Sjögren's syndrome. The decreased number of OKT8‐positive cells in primary Sjögren's syndrome was probably not caused by circulating autoantibody, since patients' sera did not react with normal OKT8‐positive cells. Functional studies using pokeweed mitogen demonstrated that T helper cell activity for immunoglobulin synthesis was contained in the OKT4‐positive subset in both normal and patients' peripheral blood lymphocytes. Removal of OKT8‐positive cells by complement‐mediated lysis did not lead to increased immunoglobulin synthesis or production of rheumatoid factor. The identification of peripheral blood lymphocyte subsets by use of monoclonal antibodies and the relationship of these subsets to tissue infiltrates and autoantibody production provide further insight into the pathogenesis of primary Sjögren's syndrome.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.