Publications & Reports

Tetraspanin CD37 Regulates beta2 Integrin-Mediated Adhesion and Migration in Neutrophils.

Wee JL, Schulze KE, Jones EL, Yeung L, Cheng Q, Pereira CF, Costin A, Ramm G, van Spriel AB, Hickey MJ, Wright MD
Department of Immunology, Monash University, Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia; Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria 3168, A

Abstract

Deciphering the molecular basis of leukocyte recruitment is critical to the understanding of inflammation. In this study, we investigated the contribution of the tetraspanin CD37 to this key process. CD37-deficient mice showed impaired neutrophil recruitment in a peritonitis model. Intravital microscopic analysis indicated that the absence of CD37 impaired the capacity of leukocytes to follow a CXCL1 chemotactic gradient accurately in the interstitium. Moreover, analysis of CXCL1-induced leukocyte-endothelial cell interactions in postcapillary venules revealed that CXCL1-induced neutrophil adhesion and transmigration were reduced in the absence of CD37, consistent with a reduced capacity to undergo beta2 integrin-dependent adhesion. This result was supported by in vitro flow chamber experiments that demonstrated an impairment in adhesion of CD37-deficient neutrophils to the beta2 integrin ligand, ICAM-1, despite the normal display of high-affinity beta2 integrins. Superresolution microscopic assessment of localization of CD37 and CD18 in ICAM-1-adherent neutrophils demonstrated that these molecules do not significantly cocluster in the cell membrane, arguing against the possibility that CD37 regulates beta2 integrin function via a direct molecular interaction. Moreover, CD37 ablation did not affect beta2 integrin clustering. In contrast, the absence of CD37 in neutrophils impaired actin polymerization, cell spreading and polarization, dysregulated Rac-1 activation, and accelerated beta2 integrin internalization. Together, these data indicate that CD37 promotes neutrophil adhesion and recruitment via the promotion of cytoskeletal function downstream of integrin-mediated adhesion.

Publication

  • Journal: Journal of immunology (Baltimore, Md. : 1950)
  • Published: 15/12/2015
  • Volume: 195
  • Issue: 12
  • Pagination: 5770-5779