Cellular source(s) of platelet-activating-factor acetylhydrolase activity in plasma

Platelet activating factor (PAF) is immediately degraded and inactivated in the bloodstream by plasma PAF acetylhydrolase (PAF-AH), Although plasma PA F-AH-like activity was secreted in vitro from various cell types such as ma crophages and hepatocytes, the exact cellular source(s) of this enzyme acti vity in vivo remains unclear. There is a naturally-occurring missense mutat ion (V279F) in the plasma PAF-AH gene in the Japanese population which resu lts in complete loss of the enzyme activity. We analyzed 52 Japanese who ha d received an allogeneic bone marrow transplant and maintained donor-derive d hematopoiesis. Ten recipients had chimeric plasma PAF-AH genotypes betwee n the donor-derived peripheral blood leukocytes and the recipient-derived e pithelial cells of buccal mucosa. Multiple regression analysis demonstrated that PAF-AH activity in plasma depended on the donor's genotype (standardi zed regression coefficient = 0.68, P < 0.0001), but not on the recipient's genotype (p = 0.48). One recipient who was a V279F homozygote in leukocytes and wild type homozygote in buccal mucosa had undetectable PAF-AH activity in plasma. We conclude that most of the PAF-AH activity in human plasma or iginates from hematopoietic lineage cells. (C) 1999 Academic Press.