PLATELETS AND THROMBOPOIESIS PAF-acetylhydrolase expressed during megakaryocyte differentiation inactivates PAF-like lipids

Platelet activating factor (PAF) and PAFlike lipids induce inflammatory responses in target cells. These lipid mediators are inactivated by PAF-acetylhydrolase (PAFAH). The PAF signaling system affects the growth of hematopoietic CD34 cells, but roles for PAF-AH in this process are unknown. Here, we investigated PAF-AH function during megakaryopoiesis and found that human CD34 cells accumulate this enzymatic activity as they differentiate toward megakaryocytes, consistent with the expression of mRNA and protein for the plasma PAF-AH isoform. Inhibition of endogenous PAF-AH activity in differentiated megakaryocytes increased formation of lipid mediators that signaled the PAF receptor (PAFR) in fully differentiated human cells such as neutrophils, as well as megakaryocytes themselves. PAF-AH also controlled megakaryocyte IIb 3-dependent adhesion, cell spreading, and mobility that relied on signaling through the PAFR. Together these data suggest that megakaryocytes generate PAF-AH to modulate the accumulation of intracellular phospholipid mediators that may detrimentally affect megakaryocyte development and function. (Blood. 2009;113:6699-6706)