Differential local and systemic regulation of the murine chemokines KC and MIP2

• Published in: Shock (Augusta, Ga.) Ga.), 2001-04, Vol.15 (4), p.278-284
• Main Authors: CALL, Douglas R, NEMZEK, Jean A, EBONG, Samuel J, BOLGOS, Gerald R, NEWCOMB, David E, WOLLENBERG, Gordon K, REMICK, Daniel G
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Blotting, Western; Chemokine CXCL1; Chemokine CXCL2; Chemokines - genetics; Chemokines - metabolism; Chemokines - pharmacology; Chemokines, CXC; Chemotactic Factors - genetics; Chemotactic Factors - metabolism; Chemotactic Factors - pharmacology; Chemotaxis, Leukocyte - drug effects; Emergency and intensive care: infection, septic shock; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation; Glycogen - toxicity; Growth Substances - genetics; Growth Substances - metabolism; Growth Substances - pharmacology; Intensive care medicine; Intercellular Signaling Peptides and Proteins; Interleukin-6 - analysis; Leukocyte Elastase - secretion; Lipopolysaccharides - pharmacology; Macrophage Activation - drug effects; Macrophages, Peritoneal - secretion; Medical sciences; Mice; Mice, Inbred BALB C; Models, Animal; Neutrophils - drug effects; Peritonitis - chemically induced; Peritonitis - genetics; Peritonitis - immunology; Peritonitis - metabolism; Rabbits; Recombinant Fusion Proteins - pharmacology; Thioglycolates - toxicity; Tumor Necrosis Factor-alpha - analysis
• ISSN: 1073-2322; 1540-0514
• DOI: 10.1097/00024382-200115040-00005

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.