4.4 Article

JAM-C is a component of desmosomes and a ligand for CD11b/CD18-mediated neutrophil transepithelial migration

期刊

MOLECULAR BIOLOGY OF THE CELL
卷 15, 期 8, 页码 3926-3937

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AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E04-04-0317

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  1. NHLBI NIH HHS [HL 54229, R01 HL072124, R01 HL054229, HL 72124] Funding Source: Medline
  2. NIDDK NIH HHS [R01 DK061379, R01 DK059888, DK 61379, DK-77640, DK 59888] Funding Source: Medline

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Neutrophil (PMN) transepithelial migration is dependent on the leukocyte 13, 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.

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