Interleukin-15 increases neutrophil adhesion onto human respiratory epithelial A549 cells and attracts neutrophils in vivo.
Interleukin-15 (IL-15) is a neutrophil agonist that plays a role in inflammatory disorders, including a variety of pulmonary diseases. Adhesion of neutrophils onto pulmonary cells is a major event leading to development of inflammation. Recently, elevated levels of IL-15 have been associated with different pulmonary diseases. There is no clear evidence that IL-15 modulates cell surface expression of adhesion molecules in neutrophils, or that IL-15 is involved in neutrophil adhesion onto pulmonary cells. Also, it is not clear if IL-15 induces a neutrophilic inflammation in vivo. This study was aimed at elucidation of these issues. Neutrophils were treated with IL-15 and cell surface expression of CD11a, CD11b, CD11c and CD18 was monitored by flow cytometry. The human respiratory epithelial A549 cell line was used as a substrate for the neutrophil adhesion assay and cell surface expression of CD50, CD54 and CD106 was monitored in IL-15-induced A549 cells. The murine air pouch model was used for investigating potential neutrophilic inflammation induced by IL-15 in vivo. IL-15 significantly increased neutrophil cell surface expression of CD11b and CD18 and up-regulated A549 cell surface expression of CD54. Moreover, A549 cells were found to express IL-15R components and adhesion of neutrophils onto A549 cells was increased when neutrophils or A549 cells were treated with IL-15. Finally, IL-15 induced neutrophilic inflammation in vivo and concentrations of IL-6 and CXCL2/MIP-2 were increased in IL-15-induced pouches. IL-15 might participate in inflammatory pulmonary diseases by attracting neutrophils, modulating cell surface expression molecules and increasing neutrophil adhesion onto pulmonary cells.
INRS-Institut Armand-Frappier, Université du Québec, Pointe-Claire, PQ H9R 1G6, Canada.
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Pelletier
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Girard
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002460:Cell Line; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019409:Interleukin-15 / Q000276:immunology*; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D039481:CD11b Antigen; D018821:CD18 Antigens; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; C508024:IL15RA protein, human; C508025:Il15ra protein, mouse; D019409:Interleukin-15; D015850:Interleukin-6; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1