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Macrophage Migration Inhibitory Factor Is Markedly Expressed in Active and Early-Stage Endometriotic Lesions

Unité d’Endocrinologie de la Reproduction (R.K., A.A.), Centre de Recherche, Hôpital Saint-François d’Assise, Centre Hospitalier Universitaire de Québec, Université Laval, Québec, Canada G1L 3L5; and The Picower Institute for Medical Research (C.N.M.), Manhasset, New York 11030

Address all correspondence and requests for reprints to: Ali Akoum, Ph.D., Unité d’Endocrinologie de la Reproduction, Center de Recherche, Hôpital Saint-François d’Assise, Center Hospitalier Universitaire de Québec, 10, rue de l’Espinay, Local D0-711, Québec, Canada G1L 3L5. E-mail: ali.akoum{at}crsfa.ulaval.ca

Abstract

The establishment of a new vascular supply is essential for the survival of endometrial tissue and its development in ectopic locations. We have previously shown that ectopic endometrial cells release an important mitogenic activity for human endothelial cells and identified macrophage migration inhibitory factor (MIF) as one of the principal bioactive molecules involved in endothelial cell proliferation. In the present study, immunohistochemical and dual immunofluorescence analyses showed that MIF is effectively expressed by endometriotic tissue, particularly in the glands, and identified endothelial cells, macrophages, and T lymphocytes as cells markedly expressing MIF in the stroma. Western blot analysis showed a single 12.5-kDa band corresponding to the known mol wt of the molecule. The highest concentrations of MIF protein in endometriotic tissue, as measured by ELISA, were found in flame-like red endometriotic lesions, compared with typical black-bluish (P < 0.01) or with white lesions (P < 0.01). Interestingly, MIF displayed a marked expression in lesions from the initial stage of endometriosis (stage I). Semiquantitative RT-PCR analysis of MIF mRNA levels in the same endometriotic tissues showed a pattern of expression comparable with that of the protein. In view of its potent proinflammatory and angiogenic properties, local production of MIF within endometrial implants, particularly in those that are highly vascularized and representing the earliest and most active forms of the disease, make plausible the involvement of this factor in the local immunoinflammatory process observed in endometriosis and the initial steps of endometriotic tissue growth and development.

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