Requirement for C-X-C chemokines (macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant) in IgG immune complex-induced lung injury
| Autor: | T P, Shanley, H, Schmal, R L, Warner, E, Schmid, H P, Friedl, P A, Ward |
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| Rok vydání: | 1997 |
| Předmět: |
Male
Chemotactic Factors Neutrophils Tumor Necrosis Factor-alpha Monokines Chemokine CXCL2 Macrophage-1 Antigen Complement C5a Rats Inbred Strains Antigen-Antibody Complex Cross Reactions Antibodies Lymphocyte Function-Associated Antigen-1 Rats Leukocyte Count Immunoglobulin G Macrophages Alveolar Animals Intercellular Signaling Peptides and Proteins Chemokines Growth Substances Bronchoalveolar Lavage Fluid Chemokines CXC Lung Peroxidase |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 158(7) |
| ISSN: | 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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