Vascular endothelial growth factors VEGF-A and VEGF-C are the main angiogenic factors that control growth of new blood and lymphatic vessels in the organism, and they also possess several immunoregulatory activities. Expression of VEGF-A and VEGF-C mRNA as well as mRNA for VEGF receptors in lymphocytes and macrophages of naive mice was investigated. Using reverse transcription and subsequent polymerase chain reaction, we found that peritoneal macrophages, thymocytes, and lymph node cells constitutively expressed VEGF-A and VEGF-C mRNA. In addition, macrophages were positive for VEGFR-1, VEGFR-2, VEGFR-3, NRP-1, and NRP-2 mRNA, whereas thymocytes and lymph node cells expressed mRNA of the same receptors except VEGFR-1. These data expand our knowledge concerning gene distribution of VEGF receptors in the organism, in particular, among the cells of the immune system. This suggests that, along with their major angiogenic properties, VEGF family members additionally might also perform important mediatory functions within the immune system.

Despite ample data on cytokine secretion in the uteroplacental interface, the influence of microenvironment cells, in particular, trophoblast cells on angiogenesis and the role of cytokines in this process remain poorly studied. We studied the influence of cytokines on the formation of tube-like structures by endothelial cells in the presence of trophoblast cells and showed that trophoblast cells suppressed the angiogenic potential of endothelial cells. Antiangiogenic cytokines IFN-γ, IL-10, TNF-α, and TGFβ via modulation of trophoblast cells stimulated the formation of tube-like structures by endothelial cells. In the co-culture of endothelial and trophoblast cells, the effects of cytokines changed and they gained additional regulatory functions.

The localization of apoptosis and expression of proapoptotic and antiapoptotic factors by the placental tissue were compared during normal pregnancy and gestosis-complicated pregnancy. The degree of apoptosis did not differ in the third trimester of normal pregnancy and gestosis-complicated pregnancy. Increased expression of Fas, caspase-8, and caspase-3 in placental tissue during normal pregnancy was shown to contribute to the suppression of angiogenesis and growth of placental tissue. No differences were found in the expression of FasL (CD95L), caspase-2, caspase-9, and Mcl-1 by placental cells during normal pregnancy and gestosis-complicated pregnancy. Increased expression of TRAIL by trophoblast cells is a protective mechanism from apoptotic signals of maternal cytotoxic lymphocytes and NK cells during gestosis.

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