engleski

The influence of HSP70 on decidual CD1a+ cells from the first trimester normal human pregnancy

Problem: The presence and/or distribution of heat shock ptrotein (HSP) 70 and its CD91 receptor at the maternal fetal interface was analyzed with particular interest in the influence of HSP70 on the function of CD1a+ dendritic cell population. Material and methods: Detection of CD91 and HSP70 was performed by immunohistology of paraffin embedded normal early pregnancy decidual tissue sections. Decidual mononuclear cells were obtained from the first trimester normal human pregnancy decudua by collagenase digestion and Lymphoprep gradient density centrifugation. Obtained cells were untreated or pretreated with increasing concentrations of HSP70 for 30 min on ice and then CD91 was labeled using monoclonal antibody and the percentage of positive cells was measured by flow cytometry. The expression of surface activation markers (CD80, CD86, HLA-DR, CCR5 and CCR7), as well as intracellular cytokines (IFN-, IL-4, IL-15, IL-17 and TNF) and chemokines (CCL3, CCL22 and CCL17) were detected in CD1a+ dendritic cells from decidual mononuclear cell suspensions recovered after 18-hours culture in the medium only or in the presence of HSP 70, respectively. Mann-Whitney U test was used to determine statistical significance between two groups of interest. Results: Intensive staining of HSP 70 was found in glandular cells of the most uterine glands, whereas weakly stained cells were observed in decidual stroma. Receptor for HSP 70, CD91 was found on approximately 20% of CD1a+ cells, besides its expression on the surface of CD14+ and CD3-CD56+ decidual leukocyte subpopulations. HSP 70 reduced anti-CD91 monoclonal antibody binding on a dose dependent manner in early pregnancy decidual CD1a+ cells. In the suspension of decidual mononuclear cells, the addition of HSP 70 did not alter activation markers expression on the surface of CD1a+ cells, but augmented the percentage of IL-15 (p=0.01) in comparison to the cells cultured in the medium only. Neither the percentages of IL-17+, IL-4+, IFN-+ or TNF-+ expressing CD1a+ cells nor the CCL3+, CCL17+ or CCL22+ expressing CD1a+ cells significantly changed under the influence of HSP 70. Final remark: Decidual dendritic CD1a+ cells express CD91 receptor for and respond to the HSP 70 stimulation in terms of IL-15 up-regulation, but they did not show other characteristics of pro-inflammatory activation. Acknowledgement: The experiments were financed by the grants of Croatian Ministry of Science, Education and Sports Grants No. 0620402-0376 and No. 0620402-0377.

heat shock protein 70; stres; dendritic cells

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