| Functional characterization of recombinant rat macrophage inflammatory protein-1 alpha and mRNA expression in pulmonary inflammation. | |
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MedLine Citation:
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PMID: 9484648 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chemokines are important inflammatory mediators that function by activating and recruiting leukocytes to an inflamed tissue. We have recently cDNA cloned the rat chemokine macrophage inflammatory protein-1 alpha (MIP-1 alpha) (1). In the present study, we characterize the biological function of recombinant MIP-1 alpha protein and describe expression of its mRNA both in vitro and in a rat model of lung inflammation. In vitro rat rMIP-1 alpha protein was chemotactic for both polymorphonuclear leukocytes (PMNs) and macrophages with maximal activity at 50 nM for both cell types. In in vivo studies, we found that intratracheal instillation of 1 and 5 micrograms of rMIP-1 alpha resulted in a significant (P < 0.05) influx of cells, primarily monocytes/macrophages, into the airspace of the lungs after 6 h. Mean numbers of lavagable PMNs were not elevated significantly (P < 0.05) for either dose of MIP-1 alpha. As a model of inflammation, rats were intratracheally instilled with 0.1 mg/kg bacterial lipopolysaccharide (LPS). Bronchoalveolar lavage (BAL) was performed 3 h later. Instillation of LPS resulted in an acute neutrophilia, but no significant change in lavagable macrophages. BAL cells from control animals (saline instilled) displayed no basal mRNA expression of either MIP-1 alpha or MIP-2 (positive control). In contrast, both MIP-1 alpha and MIP-2 mRNA levels increased markedly in BAL cells from rats instilled with LPS. The rat alveolar macrophage cell line (NR8383) also showed increased MIP-1 alpha mRNA levels in response to LPS (10 micrograms/ml) with a maximal increase after 6-8 h. The induction of MIP-1 alpha mRNA expression by LPS in NR8383 cells was attenuated by cotreatment with the antioxidants N-acetylcysteine and dimethylsulfoxide, suggesting that the induction of MIP-1 alpha mRNA by LPS is mediated via the generation of reactive oxygen species. We conclude that MIP-1 alpha is a potent chemoattractant for macrophages in vivo, and its mRNA expression in macrophages and BAL cells in response to inflammatory stimuli suggests a fundamental role in acute pulmonary inflammation. |
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Authors:
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M M Shi; I W Chong; N C Long; J A Love; J J Godleski; J D Paulauskis |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Inflammation Volume: 22 ISSN: 0360-3997 ISO Abbreviation: Inflammation Publication Date: 1998 Feb |
Date Detail:
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Created Date: 1998-03-17 Completed Date: 1998-03-17 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7600105 Medline TA: Inflammation Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 29-43 Citation Subset: IM |
Affiliation:
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Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcysteine
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pharmacology Animals Bronchoalveolar Lavage Fluid / cytology Cell Line Chemokine CCL4 Chemotaxis, Leukocyte* Dimethyl Sulfoxide / pharmacology Gene Expression Inflammation / immunology*, metabolism Lipopolysaccharides / metabolism Lung / immunology*, metabolism Lymphocyte Activation Macrophage Inflammatory Proteins / chemistry, genetics*, pharmacology* Macrophages / physiology Macrophages, Alveolar / physiology Male Neutrophils / physiology Rats Rats, Sprague-Dawley Recombinant Proteins / chemistry, pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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ES00002/ES/NIEHS NIH HHS; HL54958/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chemokine CCL4; 0/Lipopolysaccharides; 0/Macrophage Inflammatory Proteins; 0/Recombinant Proteins; 616-91-1/Acetylcysteine; 67-68-5/Dimethyl Sulfoxide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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