Microparticles and immunomodulation in pregnancy and pre-eclampsia

Abstract

Cellular microparticles are ubiquitously shed from cell membranes or secreted as endocytic vesicles called exosomes. Shed microparticles are >/=100nm in size and are generated during apoptosis or necrosis. In contrast, exosomes are smaller (<100nm), express more limited protein content and are released from late endosomes. Both membrane particles and exosomes can be detected in the circulation in non-pregnant and pregnant women. In the former, they are increased in conditions associated with systemic inflammation such as sepsis or metabolic syndrome. During pregnancy, they are also associated with pre-eclampsia and include not only particles derived from platelets, endothelium and various leukocytes but also syncytiotrophoblast-derived microparticles. Syncytiotrophoblast membrane microparticles (often called STBMs) interact with both immune and endothelial cells. They may contribute to the systemic inflammatory response of both normal and pre-eclamptic pregnancies, although inhibitory activity has also been described. Moreover, trophoblast-derived exosomes may contribute to or cause the downregulation of T cell activity that has been repeatedly observed during pregnancy. Deletion of activate T cells which express Fas ligand by Fas-expressing exosomes derived from trophoblast may contribute to immunoregulation necessary for normal pregnancy.