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Up-Regulation of CCR1 and CCR3 and Induction of Chemotaxis to CC Chemokines by IFN-γ in Human Neutrophils
Abstract
Human neutrophils (polymorphonuclear leukocytes; PMN) respond to some CXC chemokines but do not migrate to CC chemokines. Recent work has shown that chemokine receptors can be modulated by inflammatory cytokines. In this study, the effect of IFN-γ, a prototypic Th1 cytokine, on chemokine receptor expression in PMN was investigated. IFN-γ caused a rapid (∼1 h) and concentration-dependent increase of CCR1 and CCR3 mRNA. The expression of CCR2, CCR5, and CXCR1–4 was not augmented. IFN-γ-treated PMN, but not control cells, expressed specific binding sites for labeled monocyte-chemotactic protein (MCP)-3 and migrated to macrophage-inflammatory protein (MIP)-1α, RANTES, MCP-3, MIP-5/HCC2, and eotaxin. 7B11, a mAb for CCR3, inhibited the chemotactic response of IFN-γ-treated PMN to eotaxin, and aminoxypentane-RANTES blocked PMN migration to RANTES. These results suggest that the selectivity of certain chemokines for their target cells may be altered by cytokines produced within an inflammatory context. Since PMN may play a role in orienting immunity toward Th1 responses, it is possible to speculate that IFN-γ not only promotes Th1 differentiation directly, but also reorients the functional significance of Th2 effector cytokines by broadening the spectrum of their action to include PMN.
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Citations
Cited by
Neutrophil cell surface receptors and their intracellular signal transduction pathways
Futosi, K., Fodor, S., & Mócsai, A. (2013) · International Immunopharmacology · doi:10.1016/j.intimp.2013.06.034 · Cited by 642
Neutrophil chemoattractant receptors in health and disease: Double-edged swords
Metzemaekers, M., Gouwy, M., & Proost, P. (2020) · Cellular & Molecular Immunology · doi:10.1038/s41423-020-0412-0 · Cited by 570
Skelly, D. A., Squiers, G. T., McLellan, M. A., Bolisetty, M. T., Robson, P., Rosenthal, N. A., & Pinto, A. R. (2018) · Cell Reports · doi:10.1016/j.celrep.2017.12.072 · Cited by 560
Pathophysiology of acute pancreatitis
Bhatia, M., Wong, F. L., Cao, Y., Lau, H. Y., Huang, J., Puneet, P., & Chevali, L. (2005) · Pancreatology · doi:10.1159/000085265 · Cited by 544
Bleharski, J. R., Kiessler, V., Buonsanti, C., Sieling, P. A., Stenger, S., Colonna, M., & Modlin, R. L. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.7.3812 · Cited by 345
Metadata
- Authors
- Bonecchi, R., Polentarutti, N., Luini, W., Borsatti, A., Bernasconi, S., Locati, M., Power, C., Proudfoot, A., Wells, T. N. C., Mackay, C., Mantovani, A., & Sozzani, S.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-01-01
- Volume
- 162
- Issue
- 1
- Pages
- 474-479
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W4313347795
- Cited by
- 187
- References
- 0
- FWCI
- 6.44
- Type
- journal article
- Language
- en
- Open access
- closed
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- Bonecchi, R., Polentarutti, N., Luini, W., Borsatti, A., Bernasconi, S., Locati, M., Power, C., Proudfoot, A., Wells, T. N. C., Mackay, C., Mantovani, A., & Sozzani, S. (1999). Up-Regulation of CCR1 and CCR3 and Induction of Chemotaxis to CC Chemokines by IFN-γ in Human Neutrophils. The Journal of Immunology. https://doi.org/10.4049/jimmunol.162.1.474
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