Sphingomyelin: a natural modulator of membrane homeostasis and inflammation

Although membrane sphingomyelin (SPH) serves as the precursor for many signaling molecules, its presence in large amounts, and its specific localization 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 oxidative damage and phospholipase degradation. Since it contains mostly saturated longchain hydrocarbon groups, we postulate that SPH impedes the lateral propagation of the lipid peroxides by decreasing membrane fluidity, while also acting as an 'insulating' molecule. By virtue of its structural similarity to PC, it acts as a competitive inhibitor of the phospholipases, which may otherwise hydrolyze PC excessively. Because phospholipase reaction is the rate-limiting step in eicosanoid synthesis, SPH may serve as an endogenous anti-inflammatory molecule.