Epithelial ICAM-1 and ICAM-2 regulate the egression of human T cells across the bronchial epithelium.
Egression of inflammatory cells from the lung interstitium into the airway lumen is critical for the resolution of inflammation, but the underlying mechanisms of this egression are unclear. Here, we use an in vitro system, in which human T cells migrate across a bronchial epithelial monolayer, to investigate the molecules involved. We show that although inhibition of T-cell LFA-1 blocks egression by 75 +/- 5.6% (P<0.0001), inhibition of the LFA-1-ligand ICAM-1 on the epithelium only inhibits by 52.7 +/- 0.06% (P=0.0001). We, therefore, looked for other epithelial ligands for LFA-1 and demonstrate that ICAM-2, but not ICAM-3, is expressed on the bronchial epithelium. Blocking ICAM-2 inhibits egression by 50.95 +/- 10.79% (P=0.04), and blocking both ICAM-1 and ICAM-2 inhibits egression by 69.6 +/- 5.2% (P< 0.0001). Inhibition of LFA-1/ICAM-1 and ICAM-2 interactions on the basolateral epithelium does not prevent egressing T cells from adhering, polarizing, or moving over the basal epithelium, but it does prevent their recognition of the interepithelial junctions. In conclusion, we show that egression of T cells involves three distinct sequential steps: adhesion, junctional recognition, and diapedesis; we further demonstrate that ICAM-2 is expressed on the bronchial epithelium and, together with ICAM-1, has an essential function in the clearance of T cells from the lung.
Medical Research Council Laboratory of Molecular Cell Biology, University College London, London, UK. joanna.porter@ucl.ac.uk
Joanna C
JC
Porter
Alan
A
Hall
D015703:Antigens, CD / Q000378:metabolism*; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D011991:Receptors, Virus / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000037:antagonists & inhibitors / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D015703:Antigens, CD; D002227:Carbazoles; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D011412:Propanolamines; D011991:Receptors, Virus; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; C085301:adenovirus receptor; C489942:wiskostatin; D018799:Intercellular Adhesion Molecule-1; D054460:rho-Associated Kinases