Mechanisms of Junctional Adhesion Molecule‐A (JAM‐A)‐mediated neutrophil recruitment during inflammation

Abstract

JAM-A is a tight junction protein also expressed on myelomonocytic leukocytes that regulates several key processes including paracellular permeability, cell polarity, and migration. Previous studies have implicated JAM-A in regulating neutrophil (PMN) migration, however the contribution of PMN expressed JAM-A to regulating PMN recruitment in vivo is unclear. We assessed the role of JAM-A in PMN recruitment using a model of zymosan-induced peritonitis in control (WT) and JAM-A deficient (KO) mice. Following zymosan injection, KO mice exhibited reduced PMN accumulation in the peritoneal cavity after 4 hr compared to WT mice. To dissect PMN-intrinsic roles of JAM-A, WT or KO bone marrow PMN were labeled with PKH26 (red) or PKH67 (green) dyes at equal ratios and transferred via tail vein injection into peritonitic WT hosts. FACS analysis of peritoneal exudate cells revealed a reduction in KO PMN recruitment. To assess PMN-extrinsic roles of JAM-A, labeled WT PMN were transferred into peritonitic WT or KO hosts. Recruitment of transferred WT PMN was reduced in KO hosts when compared to WT hosts, which correlated with diminished peritoneal macrophage-derived KC production. These data suggest that JAM-A regulates PMN recruitment during inflammation by a multifaceted process dependent on PMN-expressed JAM-A and JAM-A on other cells that regulate chemotactic signals. (Supported by NIH AI083554, DK072564, DK59888)