Molecular mechanisms regulating CD13‐mediated adhesion |
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Authors: | Mallika Ghosh Claire Gerber M. Mamunur Rahman Kaitlyn M. Vernier Flavia E. Pereira Jaganathan Subramani Leslie A. Caromile Linda H. Shapiro |
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Affiliation: | 1. Center for Vascular Biology, University of Connecticut Health Center, , Farmington, CT, USA;2. Department of Anesthesiology, Texas Tech University Health Sciences Center, , Lubbock, TX, USA |
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Abstract: | 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 up‐regulated 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 ischaemic injury. Here, we found that 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 CD13KO animals when compared with wild‐type controls. Furthermore, adoptive transfer of wild‐type and CD13KO primary myeloid cells, or wild‐type myeloid cells pre‐treated with CD13‐blocking antibodies into thioglycollate‐challenged wild‐type recipients demonstrated fewer CD13KO or treated cells in the lavage, suggesting that CD13 expression confers a competitive advantage in trafficking. Similarly, both wild‐type and CD13KO cells were reduced in infiltrates in CD13KO 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 CD13KO mice is the result of aberrant myeloid cell subset trafficking and further defines the molecular mechanisms underlying this regulation. |
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Keywords: | adhesion molecules cell trafficking inflammation transgenic/knockout mice |
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