Modulation of PECAM-1 expression and alternative splicing during differentiation and activation of hematopoietic...

PECAM-1 (CD31) is a member of immunoglobulin gene superfamily, which is highly expressed on the surface of endothelial cells and at moderate levels on hematopoietic cells. Hematopoietic cells and platelets, like endothelial cells, express multiple isoforms of PECAM-1. However, the identity and physiological role of these isoforms during hematopoiesis remains largely unknown. Here we demonstrate that PECAM-1 expression is dramatically up regulated upon phorbol myristate acetate (PMA) or transforming growth factor (TGF)-beta1-mediated differentiation of leukemic HEL and U937 cells. The level of PECAM-1 expression did not significantly change during activation of Jurkat T cells by PMA or phytohaemagglutinin (PHA). Utilizing RT-PCR and DNA sequencing analysis, we show that the expression of PECAM-1 isoforms changes in a cell-type and lineage specific manner during cellular differentiation and activation. We identified a number of novel PECAM-1 isoforms previously not detected in the endothelium. These results demonstrate that regulated expression of PECAM-1 and its exonic inclusion/exclusion occurs during differentiation and/or activation of hematopoietic cells. Thus, different PECAM-1 isoforms may play important roles in generation of hematopoietic cells and their potential interactions with vascular endothelium.