title: The role of junctional adhesion molecule-C (JAM-C) in oxidized LDL-mediated leukocyte recruitment.
abstract: The junctional adhesion molecule-C (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. Here, we investigated the role of JAM-C in oxidized low-density lipoprotein (LDL)-mediated leukocyte recruitment. As compared with normal arteries, immunostaining of atherosclerotic vessels revealed a high expression of JAM-C in association with neointimal smooth muscle cells and the endothelium. Moreover, JAM-C was strongly up-regulated in the spontaneous early lesions in ApoE -/- mice. In vitro, cultured human arterial smooth muscle cells (HASMC) were found to express JAM-C, and oxLDL, as well as enzymatically modified LDL (eLDL) significantly up-regulated JAM-C on both HASMC and endothelial cells in a time- and dose-dependent manner. Although 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. JAM-C thereby mediated both leukocyte adhesion and leukocyte transendothelial migration upon oxLDL treatment of endothelial cells, whereas JAM-C on quiescent endothelial cells only mediates leukocyte transmigration. Thus, upon oxLDL stimulation endothelial JAM-C functions as both an adhesion, as well as a transmigration receptor for leukocytes. Taken together, JAM-C is up-regulated by oxLDL and may thereby contribute to increased inflammatory cell recruitment during atherosclerosis. JAM-C may therefore provide a novel molecular target for antagonizing interactions between vascular cells in atherosclerosis.
authors.affiliation: Experimental Immunology Branch, NCI, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Tanja
authors.initials: T
authors.lastname: Keiper
authors.forename: Nadia
authors.initials: N
authors.lastname: Al-Fakhri
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Chavakis
authors.forename: Athanasios N
authors.initials: AN
authors.lastname: Athanasopoulos
authors.forename: Berend
authors.initials: B
authors.lastname: Isermann
authors.forename: Stefanie
authors.initials: S
authors.lastname: Herzog
authors.forename: Rainer
authors.initials: R
authors.lastname: Saffrich
authors.forename: Karin
authors.initials: K
authors.lastname: Hersemeyer
authors.forename: Rainer M
authors.initials: RM
authors.lastname: Bohle
authors.forename: Judith
authors.initials: J
authors.lastname: Haendeler
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Preissner
authors.forename: Sentot
authors.initials: S
authors.lastname: Santoso
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
mesh_terms: D000368:Aged; D000818:Animals; D001011:Aorta / Q000473:pathology; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D039481:CD11b Antigen / Q000096:biosynthesis; D018821:CD18 Antigens / Q000096:biosynthesis; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000502:physiology*; D002465:Cell Movement; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000473:pathology; D004730:Endothelium, Vascular / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007136:Immunoglobulins / Q000737:chemistry / Q000502:physiology*; D007150:Immunohistochemistry; D007249:Inflammation; D007962:Leukocytes / Q000166:cytology* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D010100:Oxygen / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation
chemical_list: D039481:CD11b Antigen; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D007074:Immunoglobulin G; D007136:Immunoglobulins; C448000:JAM3 protein, human; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D010100:Oxygen