Expression and function of endothelial selectins during human development.

Leucocyte trafficking is vital for the immune defence. In adults, early tethering and rolling interactions between leucocytes and endothelial cells are mediated by P-, E- and L-selectins and their ligands. In contrast, the role of selectins in migration of mononuclear cells during fetal development in humans remains unknown. We studied the functions of endothelial E- and P-selectins and their counter-receptors during human ontogeny. Immunohistochemical stainings showed that P-selectin is expressed in megakaryocytes and endothelial cells starting from gestational weeks 7 and 11, respectively. Endothelial E-selectin appeared latest, at week 32. Real-time imaging using in vitro flow chamber assays showed that cord blood mononuclear leucocytes used E-, P- and L-selectin and PSGL-1 to roll on and adhere to endothelium under physiological shear stress. These data show that selectins are synthesized and functional before birth in humans and have the potential to mediate the emigration of mononuclear cells and inflammatory responses.