title: Ratio of local to systemic chemokine concentrations regulates neutrophil recruitment.
abstract: CXC chemokines are important regulators of local neutrophil recruitment. In this study, we examined the role of the ratio of local to systemic chemokine concentrations as a significant factor determining local neutrophil recruitment. Thioglycollate was injected intraperitoneally into BALB/c mice resulting in a dose-dependent increase in neutrophil recruitment and local inflammation, as measured by peritoneal levels of interleukin 6. At the high dose of 3% thioglycollate, antibody inhibition of the murine chemokines KC and macrophage inflammatory protein-2 caused a reduction in peritoneal neutrophil recruitment by as much as 93%. A paradoxical effect was observed with a 0.3% thioglycollate intraperitoneal challenge. In this situation, inhibition of KC resulted in a significant increase in peritoneal neutrophils, and inhibition of macrophage inflammatory protein-2 also resulted in increased peritoneal neutrophils. These results were consistent with a reverse chemotactic gradient as described by the ratio of peritoneal to plasma KC levels. A higher ratio (ie, increased peritoneal chemokines compared to plasma) resulted in increased neutrophil recruitment after either the 3% or 0.3% thioglycollate challenge. Our results demonstrate that whereas sufficient local concentrations of chemokines are necessary, a critical factor dictating local neutrophil recruitment is the ratio of the local to the systemic chemokine concentrations.
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Call
authors.forename: J A
authors.initials: JA
authors.lastname: Nemzek
authors.forename: S J
authors.initials: SJ
authors.lastname: Ebong
authors.forename: G L
authors.initials: GL
authors.lastname: Bolgos
authors.forename: D E
authors.initials: DE
authors.lastname: Newcomb
authors.forename: D G
authors.initials: DG
authors.lastname: Remick
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D054426:Chemokine CXCL2; D018925:Chemokines / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015846:Monokines / Q000276:immunology; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects; D010537:Peritoneum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013864:Thioglycolates / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D054426:Chemokine CXCL2; D018925:Chemokines; D015850:Interleukin-6; D015846:Monokines; D013864:Thioglycolates