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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.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2004 Oct 01; Vol. 173 (7), pp. 4417-24. - Publication Year :
- 2004
-
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.
- Subjects :
- Adult
CD4 Antigens physiology
Cell Membrane immunology
Cell Membrane metabolism
Cell Membrane physiology
Chemokine CCL11
Chemokine CCL5 metabolism
Chemokines, CC metabolism
Collagen immunology
Collagen metabolism
Collagen physiology
Drug Combinations
Eosinophils enzymology
Eosinophils metabolism
Extracellular Matrix enzymology
Extracellular Matrix immunology
Female
Fibrinolysin metabolism
Fibrinolysin physiology
Humans
Laminin immunology
Laminin metabolism
Laminin physiology
Male
Plasminogen metabolism
Plasminogen physiology
Proteoglycans immunology
Proteoglycans metabolism
Proteoglycans physiology
Receptors, CCR3
Signal Transduction immunology
Up-Regulation immunology
CD4 Antigens biosynthesis
Chemotactic Factors, Eosinophil physiology
Chemotaxis, Leukocyte immunology
Eosinophils cytology
Eosinophils immunology
Interleukin-16 physiology
Plasminogen Activators physiology
Receptors, Chemokine physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 173
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 15383572
- Full Text :
- https://doi.org/10.4049/jimmunol.173.7.4417