Distinct temporal patterns of macrophage-inflammatory protein-2 and KC chemokine gene expression in surgical injury.
In the present study the regulation of CXC chemokine expression was evaluated in full-thickness abdominal wounds in mice. During the first 24 h after injury, IL-1alphabeta, KC, macrophage-inflammatory protein (MIP)-2, and monocyte chemoattractant protein-1 were the predominant cytokines and chemokines produced; TNF-alpha was not detected. Chemokine mRNA expression and protein secretion occurred in two temporal stages. The first, which reached a maximum at 6 h, was associated with high levels of IL-1alpha and KC and low levels of MIP-2. This stage could be reproduced by intradermal injection of IL-1alpha or IL-1beta and was partially blocked by injection of neutralizing Ab against IL-1alpha but not IL-1beta. In animals depleted of circulating neutrophils, chemokine expression was reduced by nearly 70% during this stage. In the second stage, which peaked at 24 h after injury, modest but significant levels of IL-1beta were detected in association with low levels of KC and high levels of MIP-2. This pattern of chemokine expression could not be mimicked by injection of IL-1alpha or IL-1beta (even with prolonged exposure), although MIP-2 expression could be partially inhibited by intradermal injection of neutralizing Ab against IL-1beta. Surprisingly, neutrophil depletion before injury resulted in sustained high levels of both KC and MIP-2 expression. These observations demonstrate that these two closely related chemokines are under distinct regulatory controls in vivo that are likely to reflect the temporally ordered participation of different cell types and/or extracellular stimuli and inhibitors.
Endlich
Brian
B
Department of Immunology and Minimally Invasive Surgery Center, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Armstrong
David
D
Brodsky
Jason
J
Novotny
Michael
M
Hamilton
Thomas A
TA
D000005:Abdomen / Q000601:surgery; D000818:Animals; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D002630:Chemotactic Factors / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000276:immunology; D013997:Time Factors; D014947:Wounds and Injuries / Q000276:immunology* / Q000378:metabolism
D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1