Published online before print July 15, 2009

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(Journal of Leukocyte Biology. 2009;86:1135-1144.)
© 2009 Society for Leukocyte Biology

Ca²⁺ signaling in airway epithelial cells facilitates leukocyte recruitment and transepithelial migration

Department of Pharmacology and Pediatrics, College of Physicians & Surgeons, Columbia University, New York, New York, USA

1. Correspondence: Columbia University, Black Building 416, 650 West 168th St., New York, NY 10032, USA. E-mail: asp7{at}columbia.edu

ABSTRACT

In airway cells, TLR2 stimulation by bacterial products activates Ca²⁺ fluxes that signal leukocyte recruitment to the lung and facilitates transepithelial migration into the airway lumen. TLR2 is apically displayed on airway cells, where it senses bacterial stimuli. Biochemical and genetic approaches demonstrate that TLR2 ligands stimulate release of Ca²⁺ from intracellular stores by activating TLR2 phosphorylation by c-Src and recruiting PI3K and PLC to affect Ca²⁺ release through IP3Rs. This Ca²⁺ release plays a pivotal role in signaling TLR2-dependent NF-B activation and chemokine expression to recruit PMNs to the lung. In addition, TLR2-initiated Ca²⁺ release activates Ca²⁺-dependent proteases, calpains, which cleave the transmembrane proteins occludin and E-cadherin to promote PMN transmigration. This review highlights recent findings that demonstrate a central role for Ca²⁺ signaling in airway epithelial cells to induce proinflammatory gene transcription and to initiate junctional changes that accommodate transmigration of recruited PMNs.