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Characterization of the eosinophil chemokine RANTES in nasal polyps.
Previous studies have demonstrated that the cytokine RANTES (Regulated And Normal T cell Expressed and Secreted) has been shown to be a potent mediator of eosinophil chemotaxis in vitro and of leukocyte recruitment. Because eosinophils are the hallmark cells in nasal polyposis, we hypothesize that RANTES is locally produced within the nasal polyp microenvironment and is responsible for the eosinophil recruitment seen in nasal polyposis. To begin to test this hypothesis, we evaluated nasal polyps from 17 patients and 3 control specimens for distribution and content of RANTES using immunohistochemical techniques and enzyme-linked immunosorbent assay technology. Our immunohistochemical studies demonstrated that in nasal polyposis, RANTES antigen staining occurred predominantly within eosinophils and epithelial cells. To quantify the relative levels of RANTES in normal and nasal polyp specimens, tissue homogenates were prepared, quantified, and normalized to protein levels. We detected RANTES in all 17 nasal polyp tissue homogenates (566 +/- 16 pg/mg total protein). The RANTES levels in nasal polyp homogenates were nearly 40-fold higher than the RANTES levels in normal tissue (15.7 +/- 28.2 pg/mg total protein). Thus, it appears that increased expression of RANTES by eosinophils and epithelial cells within the nasal polyp microenvironment promotes eosinophil recruitment and activation within nasal polyps. We hypothesize that RANTES induces increased recruitment and activation of eosinophils, presumably contributing to the increased tissue changes associated with nasal polyposis.
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