TLR2-induced calpain cleavage of epithelial junctional proteins facilitates leukocyte transmigration.

ABSTRACT: Recruitment of polymorphonuclear leukocytes (PMNs) into the lungs in response to inhaled pathogens is initiated by epithelial signaling, the activation of toll-like receptors (TLRs), and the production of the chemokine interleukin-8. To reach the site of infection, PMNs must be mobilized through epithelial junctions. Here, we demonstrate that Ca(2+) fluxes generated by TLR2 signals activate calpains, Ca(2+)-dependent cysteine proteases. These activated calpains cleave the transmembrane junctional proteins occludin and E-cadherin without breaching the integrity of the epithelial barrier. Calpain inhibitors decrease PMN transepithelial migration in response to TLR2 agonists both in vitro and in a mouse model of P. aeruginosa infection. Thus, TLR2 signaling in the airway not only induces chem

SUBMITTER: Chun J 

PROVIDER: S-EPMC2768384 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature