Macrophage differentiation in the tissues of myomatous nodes, depending on MRI pattern

Abstract

Macrophage differentiation is known to be regulated by specific microenvironment invaded by these cells. However, despite numerous studies on pathogenesis of uterine leiomyoma, a common benign tumor of reproductive system, the features of macrophage polarization within myoma nodes are still scarcely studied. The aim of our work was to reveal some differentiation features of macrophages which invade the tissues of myomatous nodes in the patients with different types of uterine leiomyoma (UL) dependent on MRI patterns observed. We have performed a study of 42 patients in their reproductive age with intramural UL. All the patients were subjected to MRI of pelvic area. Twelve samples of endometrium have been taken from healthy women without any signs of UL, being used as controls. UL biopsies and endometrium in its projection served as study material. Phenotype of endometrial and UL-invading macrophages was evaluated by means of multi-color flow cytometry. Expression of Activin А and RARα mRNAs was estimated in endometrial and myoma node macrophages. Likewise, collagen type 1 mRNA expression was evaluated by means of reverse-transcription real time PCR. The collagen type 1 concentration in myomatous nodes was assessed by ELISA technique. We have revealed that peripheral blood monocytes, macrophages in endometrium, and UL nodes each consist of three different subpopulations, dependent on expression levels of expression levels of CD14 and CD16 membrane receptors. For endometrium projected onto myomatous node, the ratios of “intermediate” macrophages (CD14++CD16+), and alternatively activated macrophages (CD36+) was increased, thus exerting potentially negative effects upon reproductive functions in women with uterine leiomyoma. Immediately in myomatous tissue, we have found a shift of macrophage differentiation from ‘classic’ forms towards “intermediate” and “non-classical” macrophages associated with alternative activation. However, the percentage of scavenger receptor-expressing macrophages (CD36+, CD206+) was decreased in the myoma nodes. Enhanced expression of RARα mRNA was observed in macrophages invading the myomatous nodes, whereas Activin А synthesis was higher in the macrophages invading leiomyomas with MRI pattern of simple and degenerative nodes. Imbalance between “intermediate” and “non-classical” UL-invading macrophages was associated with fibrosis, or degenerative changes of myomatous tissues, thus, probably, representing an important pathogenetic link in development of different clinical variants of uterine leiomyoma.