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Molecular Human Reproduction, Vol. 6, No. 10, 899-906, October 2000
© 2000 European Society of Human Reproduction and Embryology


Uterine physiology

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

Louise J. Lathbury and Lois A. Salamonsen1

Prince Henry's Institute of Medical Research, PO Box 5152, Clayton, 3168, Victoria, Australia

Abstract

Significant numbers of neutrophils are found extravascularly within the endometrium 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 considered to play a crucial role in the degradation of endometrial tissue that occurs at menstruation. Latent MMP-2, MMP-3 and MMP-9 released by endometrial stromal fibroblasts and peripheral blood neutrophils were activated when the two cell types were cultured together. Tissue inhibitors of metalloproteinases (TIMP) 1 and 2 were also degraded in this system. Neutralization studies identified a role for the serine protease, elastase, in the observed activation of MMP. Although cultured endometrial neutrophils behaved similarly 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 stromal fibroblasts. This appeared to be due to an alteration in the neutrophil production of elastase and inhibitors. e.g. {alpha}1-antitrypsin, in these cultures so that active elastase was not available. Our results demonstrate that any involvement of neutrophils in the tissue destruction occurring at menstruation may be tightly regulated by the focal concentration of degradative enzymes and their respective inhibitors.

elastase/endometrium/menstruation/metalloproteinase/neutrophil

Notes

1 To whom correspondence should be addressed at: Prince Henry's Institute of Medical Research, PO Box 5152, Clayton, 3168, Victoria, Australia. E-mail: lois.salamonsen{at}med.monash.edu.au


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