Production of chemokines in vivo in response to microbial stimulation.
Members of the chemokine gene superfamily are known to play a central role in leukocyte extravasation; however, their involvement in acute inflammation in response to micro-organisms has not yet been well studied. We have therefore investigated the role of murine macrophage-inflammatory protein (muMIP) 1alpha and muMIP-2 in the inflammatory response mounted against the bacteria Salmonella enteritidis and the Sacchromyces cerevisiae cell wall component, zymosan. Leukocyte extravasation was monitored in murine s.c. air pouches. Both agonists induced accumulation of leukocytes in a dose- and time-dependent manner, with the response peaking after 4 h and declining thereafter. The inflammatory exudate comprised mainly neutrophils; however, an increase in eosinophil accumulation was also observed in response to zymosan. The production of both muMIP-1alpha and muMIP-2 increased with time in response to both the agonists, although production was more sustained in response to the bacteria. Prior treatment of mice with neutralizing Abs against muMIP-1alpha or muMIP-2, either alone or in combination, failed to attenuate the accumulation of leukocytes in response to the agonists. In contrast, the anti-muMIP-2 Abs significantly inhibited leukocyte recruitment in response to S. enteritidis in complement-deficient mice. Taken together, these data show that while muMIP-1alpha and muMIP-2 are produced in response to phagocytosis of micro-organisms in s.c. tissue, under these circumstances components of the complement pathway appear to play a dominant role in the recruitment of neutrophils.
Coates
N J
NJ
Chemokine Biology Laboratory, Department of Molecular BioSciences, University of Adelaide, Adelaide, South Australia, Australia.
McColl
S R
SR
D000818:Animals; D002021:Buffers; D002465:Cell Movement / Q000276:immunology; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology; D003182:Complement C5 / Q000172:deficiency / Q000235:genetics; D015194:Diffusion Chambers, Culture; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005122:Exudates and Transudates / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D005260:Female; D007106:Immune Sera / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D010586:Phagocytes / Q000276:immunology; D010587:Phagocytosis / Q000235:genetics; D010710:Phosphates / Q000008:administration & dosage; D012441:Saccharomyces cerevisiae / Q000276:immunology*; D012477:Salmonella enteritidis / Q000276:immunology*; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D015054:Zymosan / Q000008:administration & dosage
D002021:Buffers; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D018925:Chemokines; D003182:Complement C5; C404915:Cxcl2 protein, mouse; D007106:Immune Sera; D019402:Macrophage Inflammatory Proteins; D010710:Phosphates; D012965:Sodium Chloride; D015054:Zymosan; C018279:sodium phosphate