engleski

Expression of heat shock protein gp96 at the materno-fetal interface

PROBLEM: Heat shock proteins (HSPs), among the first proteins produced by the zygote after fertilization, are the most abundant and ubiquitous intracellular chaperons performing a multitude of housekeeping functions (ie. protein folding, facilitation of protein transport). HSPs-peptide complex "shuttle" antigenic peptides into MHC class I presentation pathway of antigen presenting cells (APCs). Recently, specific receptor (CD91) for gp96 has been identified on monocyte/macrophage linage and dendritic cells. Gp96 is a major component of the lumen of the endoplasmatic reticulum. The presence of gp96 in the extracellular milieu acts as an excellent message that alerts the APCs to physical damage of the surrounding cells (bacterial and viral infections or mechanical injury). We investigated expression of gp96 at the materno-fetal interface to gain information on its extent and possible immunological role on the implantation site. MATERIALS AND METHODS: We have examined the localization of the gp96 and its receptor CD91 by immunohistology in decidual tissue from women during the first trimester of normal pregnancy. Decidual cell isolation was accomplished by enzymatic digestion. Immunofluorescency was used to analyze the phenotype of CD91 positive cells. Controls were provided by peripheral blood lymphocytes (PBLs) from the pregnant women. RESULTS: In the decidua gp96 expression was restricted to the cytoplasm compartment of all cells. The cytoplasm of epithelial cells (apical parts) of the uterine glands, as well as extravillous trophoblastic cells, showed particularly intensive expression. Apart from the epithelial and trophoblastic cells, stromal cells and large granular lymphocytes also showed intensive staining. Some stromal cells, smooth muscular cells and vessel endothelial cells were gp96 negative. CD91 molecule was expressed on the decidual adherent cells in a much higher level than in non-adherent cell population (62 %vs. 3.8%). CD91 is expressed mostly on monocyte population in PBLs. The phenotype of CD91+ cells revealed that HLA-DR+, CD83+ and CD56+ cells express the gp96 receptor. CONCLUSIONS: Heterogeneous expression of gp96 (being most intense on trophoblast cells and glandular epithelium) at the materno-fetal interface, suggests a regulatory role of this stress protein and the ability of gp96 to mediate activation of APCs and CD56+ cells in decidua. These investigations are supported by grant No. 0062029 from Ministry of Science and Technology, Republic of Croatia.

Heat shock protein gp96; Antigen presenting cells; CD91; Decidua; CD56+ cells

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