Differential local and systemic regulation of the murine chemokines KC and MIP2.
We characterized the relative biological activity and expression of two murine chemokines that may serve as functional homologues for human IL-8, KC, and macrophage inflammatory protein 2 (MIP2). Recombinant chemokines were produced in bacterial expression systems and antibodies specific for KC or MIP2 were raised. In vitro assays showed that KC elicited 4-fold greater neutrophil chemotaxis compared with MIP2, while MIP2 elicited significantly greater release of elastase. Lipopolysaccharide- (LPS) stimulated macrophages (8 h) secreted more MIP2 (approximately 10 ng/mL) compared with KC (approximately 4 ng/ml) and expression of either murine chemokine was independent of TNFalpha or IL-1beta production. Thioglycollate (thio) and glycogen (gly) induced peritonitis produced more KC (thio = 7.1 and gly = 2.5 ng/mL) in the peritoneum compared with MIP2 (thio = 4.5 and gly = 0.3 ng/mL). Plasma KC levels were very high after either challenge (approximately 24 ng/mL), which was >50-fold more than the systemic increase in MIP2 (approximately 0.3 ng/mL). Our data demonstrate that while KC and MIP2 have similar in vitro production characteristics, KC appears to be a more potent and systemically distributed chemokine during acute in vivo inflammation, while MIP2 expression appears limited to localized expression.
Call
D R
DR
Department of Pathology, University of Michigan, Ann Arbor 48109-0602, USA.
Nemzek
J A
JA
Ebong
S J
SJ
Bolgos
G R
GR
Newcomb
D E
DE
Wollenberg
G K
GK
Remick
D G
DG
D000818:Animals; D015153:Blotting, Western; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006003:Glycogen / Q000633:toxicity; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6 / Q000032:analysis; D019272:Leukocyte Elastase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009504:Neutrophils / Q000187:drug effects; D010538:Peritonitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013864:Thioglycolates / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
C475829:CXCL1 protein, human; 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; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011993:Recombinant Fusion Proteins; D013864:Thioglycolates; D014409:Tumor Necrosis Factor-alpha; D006003:Glycogen; D019272:Leukocyte Elastase