engleski

POSSIBLE INTERACTION OF GP96 AND ITS RECEPTORS CD91 AT THE MATERNAL FETAL INTERFACE

INTRODUCTION: Heat shock proteins (HSPs) are highly conserved proteins. They are preferentially induced by a range of cellular insults including heat shock, oxidative stress, infections, nutrient deprivation and ischaemia–reperfusion injury, protecting cells from injury and promoting refolding of denatured proteins. Furthermore, cell death caused by trauma, infection, or necrosis released HSPs in the extracellular space alone or in a complex with peptides, where they can act as strong immunogens. Tissue remodelling at maternal-fetal interface is associated with necrosis of various cell types that are potential source of extracellular HSPs. They could bind to surface receptors on antigen presenting cells ; enhance expression of co-stimulatory molecules and proinflammatory response. In addition, the dominance of proinflammatory cytokines supports the cytotoxic functions of decidual lymphocytes and thus might lead to reproductive failure. The aim of our study was to evaluate the expression and distribution of gp96 and its receptor CD91 at the first trimester of normal and pathological pregnancy decidua and normal term placenta, as well as, to investigate the influence of progesterone's mediator progesterone inducing blocking factor (PIBF) on the protein and gene levels of the CD91 in decidual mononuclear cells suspensions (DMCs) isolated from normal first trimester pregnancy decidua in vitro. MATERIAL AND METHODS: Immunohistology and immunofluorescence were used to detect presence and localization of gp96 and CD91 in paraffin embedded tissue sections of the first trimester normal and pathological pregnancy decidua and the term placenta. The expression of CD91 was investigated with flow cytometry and RT-qPCR. Possible interaction of gp96 and CD91 receptor on decidual CD1a+ dendritic cells was investigated by binding assay. RESULTS: Gp96 protein was more intensively labelled in the trophoblast and uterine decidua of pathological pregnancies contrary to normal pregnancy, although the CD91 protein expression was lower. Abundant gp96 and CD91 positive cells were found in chorionic villi and trophoblast cells infiltrated the decidua of normal term placenta. The treatment with PIBF decreased the frequency of CD91+ T cells, natural killer (NK) cells and mature dendritic cells in vitro after an 18-h culture of DMCs isolated from normal first trimester pregnancy decidua. In addition, PIBF down-regulated CD91 gene expression in DMCs. Gp96 specifically on dose response manner bind to CD91 on decidual CD1a+ dendritic cells. CONCLUSION: The abundant presence of gp96 and lower expression of CD91 at the maternal-fetal interface provides a molecular basis for their interaction. However PIBF mediated down-regulation of CD91 in vitro at the protein and gene levels in DMCs suggest its role in decreasing CD91 expression during early pregnancy in vivo. The abundance expression of gp96 and CD91 at normal term placenta visualized by immunohistology during physiological progesterone damping in vivo support this observation. Acknowledgement: The experiments were financed by Croatian Ministry of Science, Education and Sports Grants No. 062- 0620402-0376, 0620402-0377 and 620402-0379.

Gp96; maternal fetal interface

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