Macrophage inflammatory protein-1 alpha mediates lung leukocyte recruitment, lung capillary leak, and early mortality in murine endotoxemia
| Autor: | T J, Standiford, S L, Kunkel, N W, Lukacs, M J, Greenberger, J M, Danforth, R G, Kunkel, R M, Strieter |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Lipopolysaccharides
Neutrophils Molecular Sequence Data Enzyme-Linked Immunosorbent Assay Pulmonary Edema Capillary Permeability Mice Animals RNA Messenger Chemokine CCL4 Lung Inflammation Base Sequence Tumor Necrosis Factor-alpha Immune Sera Macrophages Monokines Immunization Passive Macrophage Inflammatory Proteins Intercellular Adhesion Molecule-1 Shock Septic Specific Pathogen-Free Organisms Chemotaxis Leukocyte Gene Expression Regulation Cytokines Female Rabbits |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 155(3) |
| ISSN: | 0022-1767 |
| Popis: | Systemic exposure to LPS initiates a complex sequence of events resulting in organ-specific leukocyte recruitment and end-organ injury. We hypothesized that macrophage inflammatory protein-1 alpha (MIP-1 alpha), a C-C chemokine with leukocyte chemotactic and activating properties, may play an important role in lung inflammatory cell recruitment, subsequent lung injury, and mortality in endotoxemia. CD-1 mice were challenged with LPS (200 micrograms), resulting in a maximal 3.5-fold increase in neutrophils (polymorphonuclear leukocytes (PMNs)) at 6 h post-LPS, and a 2.6-fold increase in numbers of macrophages (M phi) within lung minces at 24 h. A time-dependent increase in MIP-1 alpha mRNA and protein was detected in lung after LPS treatment, with immunolocalization of MIP-1 alpha to blood and lung M phi, and the subendothelium. The pretreatment of mice with rabbit anti-MIP-1 alpha Ab resulted in a decrease in the influx of PMNs at 6 h, and influx of M phi at 24 h post-LPS challenge, an approximately 65% reduction in LPS-induced lung permeability to Evans blue, and a modest decrease in mortality at 24, but not 48 h post-LPS. Furthermore, passive immunization of mice with anti-MIP-1 alpha serum resulted in a 35% reduction in ICAM-1 mRNA levels within lung homogenates post-LPS. Finally, the pretreatment of animals with sTNFR:Fc (soluble TNF receptor:Ig construct) resulted in a 60% reduction in LPS-induced MIP-1 alpha mRNA expression within lung homogenates at 4 h post-LPS. Our studies indicate that MIP-1 alpha plays an integral role as a mediator of both PMN and M phi recruitment in murine endotoxemia. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|