Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/11625
Type: | Journal article |
Title: | Inhibition of murine neutrophil recruitment in vivo by CXC chemokine receptor antagonists |
Author: | McColl, S. Clark-Lewis, I. |
Citation: | Journal of Immunology, 1999; 163(5):2829-2835 |
Publisher: | AMER ASSOC IMMUNOLOGISTS |
Issue Date: | 1999 |
ISSN: | 0022-1767 1550-6606 |
Abstract: | In this study, we have examined the ability of chemokine receptor antagonists to prevent neutrophil extravasation in the mouse. Two murine CXC chemokines, macrophage-inflammatory protein (MIP)-2 and KC, stimulated the accumulation of leukocytes into s.c. air pouches, although MIP-2 was considerably more potent. The leukocyte infiltrate was almost exclusively neutrophilic in nature. A human CXC chemokine antagonist, growth-related oncogene (GRO)-alpha(8-73), inhibited calcium mobilization induced by MIP-2, but not by platelet-activating factor in leukocytes isolated from the bone marrow, indicating that this antagonist inhibits MIP-2 activity toward murine leukocytes. Pretreatment of mice with GROalpha(8-73) inhibited, in a dose-dependent manner, the MIP-2-induced influx of neutrophils to levels that were not significantly different from control values. Moreover, this antagonist was also effective in inhibiting the leukocyte recruitment induced by TNF-alpha, LPS, and IL-1beta. Leukocyte infiltration into the peritoneal cavity in response to MIP-2 was also inhibited by prior treatment of mice with GROalpha(8-73) or the analogue of platelet factor 4, PF4(9-70). The results of this study indicate 1) that the murine receptor for MIP-2 and KC, muCXCR2, plays a major role in neutrophil recruitment to s.c. tissue and the peritoneal cavity in response to proinflammatory agents and 2) that CXCR2 receptor antagonists prevent acute inflammation in vivo. |
Keywords: | Leukocytes Neutrophils Animals Mice, Inbred BALB C Mice Peritonitis Platelet Factor 4 Growth Substances Intercellular Signaling Peptides and Proteins Peptide Fragments Receptors, Chemokine Chemokines, CXC Chemotactic Factors Immune Sera Monokines Cell Migration Inhibition Immunization, Passive Diffusion Chambers, Culture Injections, Intraperitoneal Cell Movement Male Chemokine CXCL1 Chemokine CXCL2 |
Appears in Collections: | Aurora harvest 7 Microbiology and Immunology publications |
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