Ca2+ signaling in airway epithelial cells facilitates leukocyte recruitment and transepithelial migration.
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 PLCgamma to affect Ca2+ release through IP3Rs. This Ca2+ release plays a pivotal role in signaling TLR2-dependent NF-kappaB 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.
Chun
Jarin
J
Department of Pharmacology and Pediatrics, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA.
Prince
Alice
A
D002118:Calcium / Q000502:physiology*; D002465:Cell Movement; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000502:physiology*; D008214:Lymphocytes / Q000276:immunology*; D010766:Phosphorylation; D015398:Signal Transduction / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000378:metabolism
C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D002118:Calcium