Sphingomyelin: a natural modulator of membrane homeostasis and inflammation

Although membrane sphingomyelin (SPH) serves as the precursor for many sign aling molecules, its presence in large amounts, and its specific localizati on in the outer monolayer of the plasma membrane suggest that it may have a cytoprotective function. We propose that SPH helps maintain the integrity of the plasma membrane by protecting phosphatidylcholine (PC) against oxida tive damage and phospholipase degradation. Since it contains mostly saturat ed longchain hydrocarbon groups, we postulate that SPH impedes the lateral propagation of the lipid peroxides by decreasing membrane fluidity, while a lso acting as an 'insulating' molecule. By virtue of its structural similar ity to PC, it acts as a competitive inhibitor of the phospholipases, which may otherwise hydrolyze PC excessively. Because phospholipase reaction is t he rate-limiting step in eicosanoid synthesis, SPH may serve as an endogeno us anti-inflammatory molecule. (C) 2001 Harcourt Publishers Ltd.