Journal article
Ratio of Local to Systemic Chemokine Concentrations Regulates Neutrophil Recruitment
The American journal of pathology, Vol.158(2), pp.715-721
02/2001
Handle:
https://hdl.handle.net/2376/111621
PMCID: PMC1850325
PMID: 11159209
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.
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Details
- Title
- Ratio of Local to Systemic Chemokine Concentrations Regulates Neutrophil Recruitment
- Creators
- Douglas Ruben Call - From the Department of Pathology, University of Michigan, Ann Arbor, MichiganJean Ann Nemzek - From the Department of Pathology, University of Michigan, Ann Arbor, MichiganSamuel John Ebong - From the Department of Pathology, University of Michigan, Ann Arbor, MichiganGerald Lee Bolgos - From the Department of Pathology, University of Michigan, Ann Arbor, MichiganDavid Eric Newcomb - From the Department of Pathology, University of Michigan, Ann Arbor, MichiganDaniel George Remick - From the Department of Pathology, University of Michigan, Ann Arbor, Michigan
- Publication Details
- The American journal of pathology, Vol.158(2), pp.715-721
- Academic Unit
- Paul G. Allen School for Global Animal Health
- Publisher
- American Society for Investigative Pathology
- Identifiers
- 99900547702901842
- Language
- English
- Resource Type
- Journal article