title: Differential local and systemic regulation of the murine chemokines KC and MIP2.
abstract: 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.
authors: Department of Pathology, University of Michigan, Ann Arbor 48109-0602, USA.
authors: D R
authors: DR
authors: Call
authors: J A
authors: JA
authors: Nemzek
authors: S J
authors: SJ
authors: Ebong
authors: G R
authors: GR
authors: Bolgos
authors: D E
authors: DE
authors: Newcomb
authors: G K
authors: GK
authors: Wollenberg
authors: D G
authors: DG
authors: Remick
mesh_terms: 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
chemical_list: 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