Eotaxin Expression by Epithelial Cells and Plasma Cells in Chronic Asthma

Abstract

SUMMARY:Chemoattractants such as eotaxin are believed to play an important role in the recruitment of eosinophils into the airways in asthma. We investigated expression of eotaxin in the airway wall in a model of chronic human asthma, in which systemically sensitized mice were exposed to low mass concentrations of aerosolized antigen for 6 weeks. In these animals, the number of intraepithelial eosinophils in the airways was significantly increased 3 hours after exposure and declined by 24 hours. In parallel, immunoreactivity for eotaxin was strikingly up-regulated in airway epithelial cells and in inflammatory cells in the lamina propria. The latter were identified as plasma cells by double immunofluorescent labeling. Increased expression of eotaxin by epithelial cells and plasma cells was also demonstrated in a case of fatal human asthma. In contrast, sensitized mice that received a single exposure to a high mass concentration of aerosolized antigen exhibited delayed eosinophil recruitment, which did not correlate with eotaxin expression. Furthermore, in sensitized chronically exposed interleukin-13-deficient mice there was virtually no recruitment of eosinophils into the airways, although eotaxin expression was greater than or equal to that in wild-type mice. These results indicate that there are striking differences between acute and chronic exposure models in the time course of eotaxin expression and eosinophil recruitment. Although high eotaxin levels alone are not sufficient to cause recruitment of eosinophils into the airways, recurrent exposure may generate or up-regulate additional signals required for eosinophil chemotaxis. (Lab Invest 2002, 82:495-504).

Altered expression of microRNA in the airway wall in chronic asthma: miR-126 as a potential therapeutic target

“…We have previously shown that accumulation of intraepithelial eosinophils is related to upregulation of expression of eotaxin in the airway epithelium in response to inhalational challenge [15]. To investigate whether the mechanism of the reduction in numbers of eosinophils in antagomir-treated mice was related to inhibition of expression of eotaxin, we performed immunostaining on sections of tracheas.…”

“…Immunoperoxidase staining of formalin-fixed, paraffin-embedded sections was performed following antigen retrieval in 0.01M citrate buffer (pH 6.0), as previously described [15]. Intensity of immunoreactivity was semi-quantitatively scored as grade 0 = no staining, grade 1 = weak staining, grade 2 = moderate staining and grade 3 = strong staining.…”

Antagonism of microRNA-126 suppresses the effector function of T H 2 cells and the development of allergic airways disease

“…OBF.1/BOB.1 is essential for V(D)J recombination by directly enhancing Ig kappa gene transcription, and in OBF.1/BOB.1 Ϫ/Ϫ mice, the production of Ig isotypes is profoundly reduced (43). The increase in OBF.1/BOB.1 expression by ant-miR-126 treatment resulted in high expression of transcripts that code for Ig chains and are likely to be derived from plasma cells that infiltrate the airways wall during allergic airways inflammation (44). Recently, a critical role of OBF.1/ BOB.1 in activation of the transcriptional factor PU.1 and for T H 2 cell function has been shown in vivo.…”

CD4+ T-Lymphocytes Regulate Airway Remodeling and Hyper-Reactivity in a Mouse Model of Chronic Asthma

“…However, in our study using chronic low-dose challenge, expression of eotaxin by airway epithelium was undiminished in mice treated with anti-CD4 antibody. We have recently demonstrated up-regulation of the induction of eotaxin and other eosinophil chemoattractants in this model as compared with short-term, high-level exposure models (Kumar et al, 2002b), and we speculate that this may account for the lack of effect of administration of anti-CD4 on eosinophil recruitment.…”

“…We have previously shown that in chronically challenged mice, expression of eotaxin by airway epithelial cells is maximal 3 hours after inhalational exposure (Kumar et al, 2002b). Airway epithelium was strongly immunoreactive for eotaxin both in mice treated with control antibody and in those treated with anti-CD4.…”