Histamine influence on apoptosis in trophoblast cell cultures

Abstract

It has been demonstrated that histamine plays an important role in the pathogenesis of preeclampsia. Histamine regulates the process of differentiation of trophoblast cells; it also acts as a growth factor in malignant melanoma cells, and prevents monocytic apoptosis. Trophoblast research has shown that in preeclampsia placentas, trophoblast apoptosis is significantly increased. The aim of our study was to demonstrate the influence of histamine on the process of apoptosis in human trophoblast cell cultures. Placentas were obtained after vaginal delivery. Tissue samples were excised from placentas and, with the use of modified Kliman's method, trophoblast cell cultures were established. The cultures were incubated with dexamethasone as an apoptosis inducer 48 hours prior to apoptosis detection assays. Along with dexamethasone, selected cell cultures were incubated with histamine (1 micromol/l) or histamine (1 micromol/l) and terfenadine (from 1 to 5 micromol/l), a H(1) receptor antagonist. For apoptotic activity detection, and quantitative analysis, we used an ELISA assay. M30-Apoptosense ELISA Kit is based on the M30 monoclonal antibody that binds only the caspase-cleaved cytokeratin 18 formed during apoptosis in trophoblast cells. Our investigation showed significantly (p < 0.05) increased apoptotic activity in cultures incubated with dexamethasone, histamine and terfenadine (% of reference value, +/-SEM): up to 113.1 +/- 4.33%. Cell cultures incubated with dexamethasone and histamine only showed significantly lower apoptotic activity 90.2 +/- 5.17%. We suggest that histamine may inhibit apoptotic activity in trophoblast cell cultures via H(1) receptor. Thus histamine may regulate the process of trophoblast differentiation (via integrin aV-b3 expression, as we previously suggested), and influence cell turnover in the placenta.