Macrophage differentiation from human monocytes decreased PAF accumulation by 90% and increased PAF acetylhydrolase activity 260-fold, demonstrating a novel regulatory mechanism.
Macrophage differentiation reduces PAF accumulation via a massive increase in the degradative enzyme PAF acetylhydrolase, representing a novel mechanism for modulating inflammatory responses.
Monocytes and macrophages produce bioactive lipids, such as platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, PAF), that mediate inflammation. These cells synthesize PAF following their activation, but not constitutively. Previous studies have demonstrated that PAF accumulation is regulated by the activity of the synthetic enzymes. We observed that the accumulation of PAF in stimulated human monocytes decreased by 90% as they differentiated into macrophages. There was no decrease in the activities of the synthetic enzymes; however, the activity of the degradative enzyme, PAF acetylhydrolase, increased 260-fold. The increase in PAF acetylhydrolase activity appeared to result from a net increase in the synthesis of a new enzyme. These studies demonstrate a novel mechanism in which an increase of the degradative enzyme regulates the accumulation of PAF. This may be an important mechanism by which macrophages modulate inflammatory responses.
Elstad et al. (1989) studied this question. Macrophage differentiation vs. Monocytes was evaluated on PAF accumulation and PAF acetylhydrolase activity. Macrophage differentiation from human monocytes decreased PAF accumulation by 90% and increased PAF acetylhydrolase activity 260-fold, demonstrating a novel regulatory mechanism.