EOSINOPHIL ACCUMULATION IN RAT UTERUS FOLLOWING ESTRADIOL ADMINISTRATION IS MODULATED BY LAMININ AND ITS INTEGRIN RECEPTORS

Eosinophils accumulate into the uterus of ovariectomized rats, after t reatment with estradiol (E2). We have investigated whether this featur e is related to interactions of eosinophils with uterine extracellular matrix proteins: laminin (LM) and fibronectin (FN). Eosinophils isola ted from the peritoneal cavity of ovariectomized rats displayed estrog en receptors measured at both binding activity and mRNA levels. An inc reased number of laminin binding sites, calculated by Scatchard analys is using iodinated LM was determined in E2-treated eosinophils (70,100 +/- 28,000 sites/cell vs 21,000 +/- 5,000 sites/cell in controls). Eo binding to I-125-LM- was inhibited by the E8-LM fragment. Estradiol u p-regulated the expression in eosinophils of alpha 6 and beta 2 integr in subunits evaluated by flow-cytometry as well as by alpha 6 mRNA exp ression. After E2 treatment, eosinophils showed higher adhesiveness to LM-coated dishes (10 +/- 2 vs 56 +/- 3%) which was inhibited by monoc lonal antibodies against alpha 6, beta 1 and beta 2 integrins and by t he steroid antagonist tamoxifen. These monoclonal antibodies also bloc ked the attachment of stimulated eosinophils to uterine cryostat secti ons obtained from spayed rats previously treated with estradiol. We di d not detect any apparent influence of E2 on basal eosinophil adherenc e or binding to FN although alpha 4 and alpha 5 integrin subunits were expressed in eosinophils. Expression of laminin and merosin in the ut erus was determined immunohistochemic ally. Our results suggest that i ntegrin-laminin interactions may contribute to the preferential eosino phil recruitment in vivo.