In airway cells, TLR2 stimulation by bacterial products activates Ca 2+ 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 Ca 2+ from intracellular stores by activating TLR2 phosphorylation by c-Src and recruiting PI3K and PLCγ to affect Ca 2+ release through IP3Rs. This Ca 2+ release plays a pivotal role in signaling TLR2-dependent NF-κB activation and chemokine expression to recruit PMNs to the lung. In addition, TLR2-initiated Ca 2+ release activates Ca 2+ -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 Ca 2+ signaling in airway epithelial cells to induce proinflammatory gene transcription and to initiate junctional changes that accommodate transmigration of recruited PMNs. Footnotes Abbreviations: ADAM 17=a disintegrin and metallopeptidase domain 17, Capn4=calpain 4, CINC=cytokine-induced neutrophil chemoattractant, CSS1=c alpain small subunit 1, Cx=connexin, DAG=diacylglycerol, EF=helix-loop-helix structural domain, ER=endoplasmic reticulum, IKK=IκB kinse, IP3R=inositol (1,4,5)-trisphosphate receptor, IRAK=IL-1R-associated kinase, KC=keratinocyte-derived chemokine, MLCK=myosin light chain kinase, MMP=matrix metalloproteinase, MUC-2=mucine 2, P3C=Pam 3Cys-SK4, PAMP=pathogen-associated molecular pattern, PH=pleckstrin homology, PKC=protein kinase C, PLCγ=phospholipase C γ, PMN=polymorphonuclear leukocyte, PRR=pattern recognition receptor, siRNA=small interfering RNA, TIR=Toll/IL-1R, Trif=TIR domain-containing adaptor-inducing IFN-β, TRPC=transient receptor potential channel, ZO-1=zona occludens 1 Received January 28, 2009. Revision received April 22, 2009. Accepted May 9, 2009. Society for Leukocyte Biology
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Ca2+ signaling in airway epithelial cells facilitates leukocyte recruitment and transepithelial migration
Chun, Jarin; Prince, Alice
Follow Journal of Leukocyte Biology
, Volume 86 (5): 1135
Fed of American Socs for Experimental Biology – Nov 1, 2009
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