Molecular Mechanisms Regulating CD13-Mediated Adhesion.

Immunology

PubMedID: 24627994

Ghosh M, Gerber C, Rahman MM, Vernier KM, Pereira FE, Subramani J, Caromile LA, Shapiro LH. Molecular Mechanisms Regulating CD13-Mediated Adhesion. Immunology. 2014;.
CD13/Aminopeptidase N is a transmembrane metalloproteinase that is expressed in many tissues where it regulates various cellular functions. In inflammation, CD13 is expressed on myeloid cells, is upregulated on endothelial cells at sites of inflammation and mediates monocyte/endothelial adhesion by homotypic interactions. In animal models the lack of CD13 alters the profiles of infiltrating inflammatory cells at sites of ischemic injury. Here, we found CD13 expression is enriched specifically on the pro-inflammatory subset of monocytes, suggesting that CD13 may regulate trafficking and function of specific subsets of immune cells. To further dissect the mechanisms regulating CD13-dependent trafficking we used the murine model of thioglycollate-induced sterile peritonitis. Peritoneal monocytes, macrophages and dendritic cells were significantly decreased in inflammatory exudates from global CD13(KO) animals when compared to wild type controls. Furthermore, adoptive transfer of wild type and CD13(KO) primary myeloid cells, or wild type myeloid cells pretreated with CD13 blocking antibodies into thioglycollate-challenged wild type recipients demonstrated fewer CD13(KO) or treated cells in the lavage, suggesting that CD13 expression confers a competitive advantage in trafficking. Similarly, both wild type and CD13(KO) cells were reduced in infiltrates in CD13(KO) recipients, confirming that both monocytic and endothelial CD13 contribute to trafficking. Finally, murine monocyte cell lines expressing mouse/human chimeric CD13 molecules demonstrated that the C-terminal domain of the protein mediates CD13 adhesion. Therefore, this work verifies that the altered inflammatory trafficking in CD13(KO) mice e is the result of aberrant myeloid cell subset trafficking and further defines the molecular mechanisms underlying this regulation. This article is protected by copyright. All rights reserved.