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The Aminopeptidase CD13 Induces Homotypic Aggregation in Neutrophils and Impairs Collagen Invasion.

Published version
Peer-reviewed

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Authors

Fiddler, Christine A 
Parfrey, Helen 
Cowburn, Andrew S 
Luo, Ding 
Nash, Gerard B 

Abstract

Aminopeptidase N (CD13) is a widely expressed cell surface metallopeptidase involved in the migration of cancer and endothelial cells. Apart from our demonstration that CD13 modulates the efficacy of tumor necrosis factor-α-induced apoptosis in neutrophils, no other function for CD13 has been ascribed in this cell. We hypothesized that CD13 may be involved in neutrophil migration and/or homotypic aggregation. Using purified human blood neutrophils we confirmed the expression of CD13 on neutrophils and its up-regulation by pro-inflammatory agonists. However, using the anti-CD13 monoclonal antibody WM-15 and the aminopeptidase enzymatic inhibitor bestatin we were unable to demonstrate any direct involvement of CD13 in neutrophil polarisation or chemotaxis. In contrast, IL-8-mediated neutrophil migration in type I collagen gels was significantly impaired by the anti-CD13 monoclonal antibodies WM-15 and MY7. Notably, these antibodies also induced significant homotypic aggregation of neutrophils, which was dependent on CD13 cross-linking and was attenuated by phosphoinositide 3-kinase and extracellular signal-related kinase 1/2 inhibition. Live imaging demonstrated that in WM-15-treated neutrophils, where homotypic aggregation was evident, the number of cells entering IL-8 impregnated collagen I gels was significantly reduced. These data reveal a novel role for CD13 in inducing homotypic aggregation in neutrophils, which results in a transmigration deficiency; this mechanism may be relevant to neutrophil micro-aggregation in vivo.

Description

Keywords

Adult, Antibodies, Monoclonal, CD13 Antigens, Cell Polarity, Cells, Cultured, Chemotaxis, Leukocyte, Collagen Type I, Humans, N-Formylmethionine Leucyl-Phenylalanine, Neutrophils

Journal Title

PLoS One

Conference Name

Journal ISSN

1932-6203
1932-6203

Volume Title

11

Publisher

Public Library of Science (PLoS)
Sponsorship
Medical Research Council (G0900329)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
This work was funded by a Medical Research Council Research Training Fellowship to CAF (G0900329), Addenbrooke’s Charitable Trust (ACT), CUHNHSFT, Papworth Hospital NHS Foundation Trust and the NIHR Cambridge Biomedical Research Centre. CAF received a Raymond and Beverly Sackler Studentship.