Junctional Adhesion Molecules (JAMs) Antibody Review

 

 

 

Introduction

  • Junctional adhesion molecules (JAMs), Ca2+-independent immunoglobulin-like cell-cell adhesion molecules, are immunoglobulin superfamily (IgSF) proteins expressed at cell junctions in epithelial and endothelial cells as well as on the surface of leukocytes, platelets, and erythrocytes. Evidence suggests JAM proteins are important for a variety of cellular processes, including tight junction assembly, leukocyte transmigration, platelet activation, angiogenesis and virus binding. PMID: 15820556, PMID: 14519386, PMID: 11739175, PMID: 10544206, PMID: 12400007

JAM-A/JAM-1

  • JAM-A has been implicated in the assembly of other epithelial tight junctions. PMID: 16859655

  • JAM-A plays an important role in leukocyte diapedesis. PMID: 16857733

  • JAM-A, a member of the immunoglobulin superfamily expressed at endothelial and epithelial tight junctions, is involved in platelet activation, leukocyte transmigration, and angiogenesis. PMID: 15977176

  • JAM-A is a cell-surface glycoprotein that localizes to intercellular junctions and associates with intracellular proteins via PSD95-Dlg-ZO1-binding residues. PMID: 15657074

  • JAM-1 is specifically localized at the tight junctions of epithelial and endothelial cells and is involved in the regulation of junctional integrity and permeability. PMID: 15065765

  • JAM-1 is a ligand of the beta(2) integrin LFA-1 involved in transendothelial migration of leukocytes. PMID: 11812992

  • JAM-1, a receptor for a platelet-activating antibody, is the human homolog of the junctional adhesion molecule. PMID: 11171323

JAM-C/JAM-3

  • JAM-C) is involved in leukocyte transendothelial migration and it can form homophilic (JAM-C/JAM-C) and heterophilic interactions with the leukocyte integrin alpha(M)beta(2). PMID: 16767690

  • JAM-C was recently shown to be a counter receptor for the leukocyte beta2-integrin Mac-1 (CD11b/CD18), thereby mediating interactions between vascular cells, particularly in inflammatory cell recruitment. PMID: 16195363

  • JAM-C is a component of desmosomes and a ligand for CD11b/CD18-mediated neutrophil transepithelial migration. PMID: 15194813, PMID: 15065765

  • JAM-3 is a type I transmembrane glycoprotein containing two Ig-like domains. PMID: 12208882

JAM-4

  • JAM4 has been identified as a protein that interacts with membrane-associated guanyl kinase inverted (MAGI)-1 and is reported to be expressed on podocytes. PMID: 16118391

  • JAM4 belongs to the immunoglobulin superfamily and mediates Ca2+-independent adhesion. PMID: 12940823

Normal Expression

  • F11 receptor (F11R/JAM) is a member of the immunoglobulin superfamily localized on the membrane surface of human platelets and a component of tight junctions of endothelial and epithelial cells. PMID: 15823866, PMID: 12428104

  • JAM-A and AF-6 were expressed at relatively high levels early in development when adherens junctions form, but before tight junctions form. Expression of JAM-A and the AF-6 isoforms actually decreased when tight junctions were forming and expanding. PMID: 16859655

  • JAM-A is prominently expressed in embryonic vasculature and the epithelial components of several organ systems and may have an important role in their development. PMID: 15977176

  • Recombinant JAM-1, when expressed in Chinese hamster ovary (CHO) cells, localized to the cell membrane with intense staining where two adjacent cells actually made contact with each other, suggesting that, similar to murine JAM, human JAM-1 may also localize at the cell-cell junction. PMID: 11171323

  • expression of JAM-A was observed in the tight junctions of rabbit corneal endothelium in a localization pattern identical with that of ZO-1, a known marker of the tight junction and binding partner of JAM-A. Expression of related proteins JAM-C and CAR (Coxsackie and adenovirus receptor) was also observed in the corneal endothelium, but their distribution was diffuse and not limited to the tight junction. PMID: 16723450

  • antibodies to JAM-2 stain high endothelial venules (HEVs) within lymph nodes and Peyer patches of adult mice. JAM-2 is expressed on HEVs in human tonsil and on a subset of human leukocytes. PMID: 12239159

  • 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. PMID: 11823489

  • antibodies specific for JAM-2 stain high endothelial venules and lymphatic vessels in lymphoid organs, and vascular structures in the kidney. Using real time video microscopy, we show that JAM-2 is localized within minutes to the newly formed cell-cell contact. PMID: 11053409

  • under quiescent conditions, JAM-C predominantly localized to interendothelial cell-cell contacts in close proximity to zonula occludens-1 (ZO-1), oxLDL treatment induced a disorganization of JAM-C localization that was no more restricted to the interendothelial junctions. PMID: 16195363

  • JAM4 was detected by immunomicroscopy at the apical membrane of normal podocytes. PMID: 16118391

  • JAM4 was localized at TJs but also on apical membranes of epithelial cells in jejunum, ileum, and renal proximal tubules. In Madine Darby canine kidney (MDCK) cells, the localization of JAM4 at TJs depended on the first Ig-loop and did not require the MAGI-1-interacting region. PMID: 12940823

  • JAM4 was colocalized with ZO-1 in kidney glomeruli and in intestinal epithelial cells. PMID: 12773569

Abnormal Expression

  • In MS abnormal JAM-A expression was found in active (46%) and inactive lesions (21%), comparable to previous data using ZO-1. However, a lower level of TJ abnormality was found in MS NAWM using JAM-A (3%) compared to ZO-1 (13%). JAM-B was strongly expressed on a small number of large blood vessels in control and MS tissues but at too low a level for quantitative analysis. PMID: 17024496

  • JAM4 immunostaining was focally increased in the podocytes in PAN nephropathy but not in ANA nephropathy. PMID: 16118391

Function

  • JAM-C expressed by endothelial cells contributes to the pathophysiology of acute pancreatitis and could be considered a target for clinical applications. PMID: 16767690

  • interactions with JAM-B and -C are essential for development of cutaneous inflammation. PMID: 16297198

  • JAM-B and JAM-C undergo heterophilic interaction in cell-cell contacts and that JAM-C is recruited and stabilized in junctional complexes by JAM-B. PMID: 16093349

  • JAM-2 affects endothelial cell junctions by its regulated clustering at intercellular contacts, and they support a role for JAM-2, and possibly JAM-3, in tight junction formation of endothelial cells. PMID: 12953056

  • JAM-A and its binding partner AF-6 are expressed in tight junctions of the corneal endothelium and that JAM-A has a major role in maintaining the corneal endothelial barrier function. PMID: 16723450

  • Junctional adhesion molecule 1 is a functional receptor for feline calicivirus. PMID: 16611908

  • JAM-C participates in the later steps of the leukoendothelial adhesion cascade. PMID: 15879142

Applications

 

Electron Microscopy (EM)

  • By immunoelectron microscopy, the signals for JAM4 were detected at the free apical membrane of the podocytes with effaced foot processes. PMID: 16118391

Functional Assay (FA)

  • Treatment with a monoclonal antibody directed against JAM-C reduces tumor growth and infiltration of macrophages into tumors. The antibody decreases angiogenesis in the model of hypoxia-induced retinal neovascularization in vivo and vessel outgrowth from aortic rings in vitro. PMID: 15994945

  • In assays of PMN transepithelial migration, both JAM-C mAbs and JAM-C/Fc chimeras significantly inhibited the rate of PMN transmigration. PMID: 15194813

  • anti-JAM-2 antibody, or a soluble JAM-2 molecule, blocks the transmigration of primary human peripheral blood leukocytes across human umbilical vein endothelial cells expressing endogenous JAM-2. PMID: 12239159

  • purified JAM-3 or antibodies against JAM-3 blocked the platelet-neutrophil interaction, indicating that platelet JAM-3 serves as a counterreceptor for Mac-1 mediating leukocyte-platelet interactions. PMID: 12208882

Immunocytochemistry (ICC)

  • Immunocytochemistry and semiquantitative confocal microscopy for JAM-A and beta-catenin was performed on snap-frozen sections from MS cases (n = 11) and controls (n = 6). PMID: 17024496

Immunofluorescence (IF)

  • Immunofluorescence confocal microscopy was used to investigate expression of JAM-A and the related proteins JAM-C, CAR, and AF-6 in the rabbit corneal endothelium. PMID: 16723450

  • Immunofluorescence analysis revealed an upregulation of JAM-A on early atherosclerotic endothelium of carotid arteries from apolipoprotein E-deficient (apoE-/-) mice fed an atherogenic diet. PMID: 15681301

  • Immunofluorescence confocal analysis of staged embryos and synchronized cell clusters revealed JAM-1 recruitment to cell contact sites occurred predominantly during the first hour after division to the eight-cell stage, earlier than any other TJ protein analysed to date in this model and before E-cadherin adhesion and cell polarization. PMID: 15494378