title: JAM-C is a component of desmosomes and a ligand for CD11b/CD18-mediated neutrophil transepithelial migration.
abstract: Neutrophil (PMN) transepithelial migration is dependent on the leukocyte beta(2) integrin CD11b/CD18, yet the identity of epithelial counterreceptors remain elusive. Recently, a JAM protein family member termed JAM-C was implicated in leukocyte adhesive interactions; however, its expression in epithelia and role in PMN-epithelial interactions are unknown. Here, we demonstrate that JAM-C is abundantly expressed basolaterally in intestinal epithelia and localizes to desmosomes but not tight junctions. Desmosomal localization of JAM-C was further confirmed by experiments aimed at selective disruption of tight junctions and desmosomes. In assays of PMN transepithelial migration, both JAM-C mAbs and JAM-C/Fc chimeras significantly inhibited the rate of PMN transmigration. Additional experiments revealed specific binding of JAM-C to CD11b/CD18 and provided evidence of other epithelial ligands for CD11b/CD18. These findings represent the first demonstration of direct adhesive interactions between PMN and epithelial intercellular junctions (desmosomes) that regulate PMN transepithelial migration and also suggest that JAM-C may play a role in desmosomal structure/function.
authors.affiliation: Epithelial Pathobiology Research Unit, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia 30322, USA. kzen@emory.edu
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
authors.forename: Brian A
authors.initials: BA
authors.lastname: Babbin
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: John B
authors.initials: JB
authors.lastname: Whelan
authors.forename: Asma
authors.initials: A
authors.lastname: Nusrat
authors.forename: Charles A
authors.initials: CA
authors.lastname: Parkos
mesh_terms: D020106:Acrylamide / Q000494:pharmacology; D039481:CD11b Antigen / Q000378:metabolism*; D018821:CD18 Antigens / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000378:metabolism* / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D003896:Desmosomes / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis* / Q000378:metabolism* / Q000494:pharmacology; D007382:Intermediate Filaments / Q000187:drug effects; D007413:Intestinal Mucosa / Q000276:immunology; D008565:Membrane Proteins / Q000032:analysis* / Q000378:metabolism* / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*
chemical_list: D039481:CD11b Antigen; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C448000:JAM3 protein, human; D008565:Membrane Proteins; D020106:Acrylamide; D004533:Egtazic Acid