PMID:9120305
| Citation |
Shanley, TP, Schmal, H, Warner, RL, Schmid, E, Friedl, HP and Ward, PA (1997) Requirement for C-X-C chemokines (macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant) in IgG immune complex-induced lung injury. J. Immunol. 158:3439-48 |
|---|---|
| Abstract |
The C-X-C chemokines of the IL-8 family possess potent chemotactic activity for neutrophils, but their in vivo role in inflammatory responses is not well understood. In the IgG immune complex-induced model of acute lung inflammatory injury in the rat we have evaluated the roles of two rat chemokines, macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC). Both mRNA and protein for MIP-2 and CINC appeared in a time-dependent manner after initiation of IgG immune complex deposition in lung. There exists a 69% homology between the amino acid sequences for these proteins, and we found cross-reactivity between polyclonal Abs raised to these chemokines. By purifying the blocking Abs using double affinity methods (with Ag-immobilized beads), this cross-reactivity was removed. Individually, anti-MIP-2 and anti-CINC Ab significantly reduced lung injury (as measured by 125I-labeled albumin leakage from the pulmonary vasculature) and reduced neutrophil accumulation in the lung (as determined by myeloperoxidase (MPO content) and neutrophil counts in bronchoalveolar lavage (BAL) fluids); however, no change in TNF-alpha levels in BAL fluids was found. Chemotactic activity in BAL fluids collected 2 h after injury from animals undergoing immune complex deposition could be shown to be chiefly due to the combined contributions of MIP-2 (39%), CINC (28%), and C5a (21%). When either MIP-2 or CINC was blocked in vivo, up-regulation of Mac-1 expression on neutrophils obtained from BAL fluids was significantly reduced. These data suggest that, in the model studied, both MIP-2 and CINC contribute significantly to the influx of neutrophils and their activation. |
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| Keywords |
Animals; Antibodies/pharmacology; Antigen-Antibody Complex/toxicity; Bronchoalveolar Lavage Fluid/cytology; Bronchoalveolar Lavage Fluid/immunology; Chemokine CXCL2; Chemokines/genetics; Chemokines/immunology; Chemokines/physiology; Chemokines, CXC; Chemotactic Factors/genetics; Chemotactic Factors/immunology; Chemotactic Factors/physiology; Complement C5a/physiology; Cross Reactions; Growth Substances/genetics; Growth Substances/immunology; Growth Substances/physiology; Immunoglobulin G/toxicity; Intercellular Signaling Peptides and Proteins; Leukocyte Count; Lung/enzymology; Lung/immunology; Lung/pathology; Lymphocyte Function-Associated Antigen-1/biosynthesis; Macrophage-1 Antigen/biosynthesis; Macrophages, Alveolar/immunology; Macrophages, Alveolar/metabolism; Male; Monokines/genetics; Monokines/immunology; Monokines/physiology; Neutrophils/immunology; Neutrophils/metabolism; Peroxidase/metabolism; Rats; Rats, Inbred Strains; Tumor Necrosis Factor-alpha/metabolism |
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