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Use of monoclonal antibodies to assess expression of anaphylatoxin receptors in rat and murine models of lung inflammation.

Authors: Tschernig, T  Kiafard, Z  Dibbert, C  Neumann, D  Zwirner, J 
Citation: Tschernig T, etal., Exp Toxicol Pathol. 2007 Aug;58(6):419-25. Epub 2007 Jun 1.
Pubmed: (View Article at PubMed) PMID:17544263
DOI: Full-text: DOI:10.1016/j.etp.2007.03.004

The anaphylatoxins C3a and C5a are involved in the pathophysiology of microbial as well as allergic inflammation in the lungs. Besides their expression in leukocytes, receptors for C3a and C5a (C3aR and C5aR) have been noted in alveolar and bronchial epithelial cells, bronchial smooth muscle cells as well as in vascular endothelial and smooth muscle cells of normal and inflamed human and murine lungs. Recently, however, expression of anaphylatoxin receptors in parenchymal cells of the lung (and kidney) has been challenged. Using well-characterized monoclonal antibodies (mabs) against murine and rat anaphylatoxin receptors, we reexamined the pulmonary distribution of C3aR and C5aR. Immunohistochemistry was performed on frozen sections of lung tissues from normal mice and rats as well as from animals subjected to lipopolysaccharide (LPS)-induced inflammation or from MRL/lpr mice suffering from autoimmune disease. Furthermore, ovalbumin (OVA)-induced models of allergic asthma in the rat and mouse were investigated. Prominent expression of both anaphylatoxin receptors was detectable in resident as well as infiltrating leukocytes. No C3aR protein was observed in alveolar macrophages. Upon LPS- and OVA-challenge as well as in autoimmune inflammation, numbers of infiltrating leukocytes expressing prominent amounts of anaphylatoxin receptors increased. Even under these highly inflammatory conditions, however, expression of C3aR and C5aR was not inducible in parenchymal cells. Thus, our findings identify infiltrating leukocytes as a prominent source of anaphylatoxin receptors in inflamed lungs. A direct involvement of parenchymal cells in anaphylatoxin-mediated pulmonary inflammation is unlikely.

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CRRD Object Information
CRRD ID: 5129560
Created: 2011-04-04
Species: All species
Last Modified: 2011-04-04
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.