In-vitro studies of the potential role of neutrophils in the process of menstruation

Significant numbers of neutrophils are found extravascularly within the end ometrium only during the immediate premenstrual and menstrual phases of the cycle. In this study we investigated the effect of neutrophil products on the synthesis and activation of matrix metalloproteinases (MMP), enzymes co nsidered to play a crucial role in the degradation of endometrial tissue th at occurs at menstruation. Latent MMP-2, MMP-3 and MMP-9 released by endome trial stromal fibroblasts and peripheral blood neutrophils were activated w hen the two cell types were cultured together. Tissue inhibitors of metallo proteinases (TIMP) 1 and 2 were also degraded in this system. Neutralizatio n studies identified a role for the serine protease, elastase, in the obser ved activation of MMP. Although cultured endometrial neutrophils behaved si milarly to peripheral blood neutrophils in their ability to release latent MMP-9 and elastase, no active forms of MMP-2. MMP-3 and MMP-9 were detected in supernatant from co-cultures containing endometrial neutrophils and str omal fibroblasts. This appeared to be due to an alteration in the neutrophi l production of elastase and inhibitors, e.g. alpha 1-antitrypsin, in these cultures so that active elastase was not available. Our results demonstrat e that any involvement of neutrophils in the tissue destruction occurring a t menstruation may be tightly regulated by the focal concentration of degra dative enzymes and their respective inhibitors.