IL-16 activates plasminogen-plasmin system and promotes human eosinophil migration into extracellular matrix via CCR3-chemokine-mediated signaling and by modulating CD4 eosinophil expression.

TitleIL-16 activates plasminogen-plasmin system and promotes human eosinophil migration into extracellular matrix via CCR3-chemokine-mediated signaling and by modulating CD4 eosinophil expression.
Publication TypeJournal Article
Year of Publication2004
AuteursFerland, C, Flamand, N, Davoine, F, Chakir, J, Laviolette, M
JournalJ Immunol
Volume173
Issue7
Pagination4417-24
Date Published2004 Oct 01
ISSN0022-1767
KeywordsAdult, CD4 Antigens, Cell Membrane, Chemokine CCL11, Chemokine CCL5, Chemokines, CC, Chemotactic Factors, Eosinophil, Chemotaxis, Leukocyte, Collagen, Drug Combinations, Eosinophils, Extracellular Matrix, Female, Fibrinolysin, Humans, Interleukin-16, Laminin, Male, Plasminogen, Plasminogen Activators, Proteoglycans, Receptors, CCR3, Receptors, Chemokine, Signal Transduction, Up-Regulation
Abstract

Increased eosinophil counts are a major feature of asthmatic airways. Eosinophil recruitment requires migration through epithelium and tissue extracellular matrix by activation of proteases. We assessed the capacity of IL-16, a CD4(+) cell chemotactic factor, to induce migration of eosinophils through a reconstituted basement membrane and evaluated the proteases, mediators, and receptors involved in this migration. IL-16 added to lower chambers of Invasion Chambers elicited eosinophil migration through Matrigel. This effect was decreased by inhibition of the plasminogen-plasmin system (Abs against urokinase plasminogen activator receptor or plasminogen depletion), but not by anti-matrix metalloproteinase-9 Abs. Abs against CD4 also inhibited IL-16-induced eosinophil migration. At the baseline level, few eosinophils (4.6% positive cells with a mean fluorescence of 0.9) expressed surface membrane CD4, while most permeabilized eosinophils (68% positive cells with a mean fluorescence of 18) express the CD4 Ag. TNF-pretreatment increased surface membrane CD4(+) expression by 6-fold as previously described, and increased IL-16-induced cell migration by 2.2-fold. Incubation of eosinophils with IL-16 also increased surface membrane CD4 expression by 5.4-fold, supporting the role of CD4 as receptor for IL-16. Abs against CCR3, eotaxin, or RANTES blocked IL-16-induced migration. In conclusion, IL-16 promotes eosinophil migration in vitro, by activating the plasminogen-plasmin system and increasing the membrane expression of its receptor. This effect is initiated via CD4 and mediated via the release of CCR3 ligand chemokines. Interestingly, most eosinophils express intracellular CD4. Hence, IL-16 may play an important role in the recruitment of blood eosinophils to the bronchial mucosa of asthmatics.

DOI10.4049/jimmunol.173.7.4417
Alternate JournalJ. Immunol.
PubMed ID15383572