期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 86, 期 3, 页码 671-680出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.1008638
关键词
chemokines; migration; cytokines
资金
- European Union
- Interuniversity Attraction Poles ProgramBelgian State-Belgian Science Policy
- Fund for Scientific Research of Flanders (FWD-Vlaanderen, Belgium)
- Concerted Research Actions of the Regional Government of Flanders
- Center of Excellence of the University of Leuven [EF/05/15]
During inflammatory reactions, endogenously produced cytokines and chemokines act in a network and interact with hormones and neurotransmitters to regulate host immune responses. These signaling circuitries are even more interfaced during infections, when microbial agonists activate TLR, RLR, and NLR receptors. On the basis of the discovery of synergy between chemokines for neutrophil attraction, we extend here this phenomenon between the chemokine MCP-1/CCL2 and the GPCR ligand fMLP or the TLR4 agonist LPS on monocytes. In fact, the bacterial tripeptide fMLP, but not the cytokines IL-1 beta or IFN-gamma, significantly and dose-dependently synergized with CCL2 in monocyte chemotaxis. Furthermore, LPS rapidly induced the expression of IL-8/CXCL8 but not of the CCL2 receptor CCR2 in monocytic cells. In turn, the induced CXCL8 synergized with CCL2 for mononuclear cell chemotaxis, and the chemotactic effect was mediated by CXCR1/CXCR2, because CXCL8 receptor antagonists or antibodies were capable of blocking the synergy, while keeping the responsiveness to CCL2 intact. These data recapitulate in vitro the complexity of innate immune regulation, provide a novel mechanism of enhancing monocyte chemotaxis during bacterial infections with gram-negative bacteria and demonstrate the importance of local contexts in inflammatory and infectious insults. J. Leukoc. Biol. 86: 671-680; 2009.
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