PAF-mediated pulmonary edema: a new role for acid sphingomyelinase and ceramide

Nat. Med. 10, 155-160 (2004)

Speaker: 蘇玲瑤

Commentator: 余俊強 老師

Time: 13:00-14:00 March 31, 2004

Place: Room 601

Abstract:

    Pulmonary edema caused by increased vascular permeability is an important clinical problem that is difficult to treat. Recently, platelet-activating factor (PAF), a proinflammatory phospholipid mediator is shown to play an important role in many models of pulmonary edema such as those induced by lipopolysaccharides (LPS), antigen, or pulmonary as well as intestinal ischemia-reperfusion (1). But the mechanisms of the PAF-induced edema formation are largely unknown. Using the isolated perfused lung (IPL) model, the authors show that PAF triggers edema by increasing microvascular permeability through two independent mechanisms: acid sphingomyelinase (ASM)- dependent production of ceramide, and activation of the cyclooxygenase pathway (2). The increased extracellular ASM activity and ceramide content are observed after PAF treatment and result in edema formation. Furthermore, ceramide-specific antibodies or xanthogenate D609, an agent that interferes ceramide biosynthesis, attenuate pulmonary edema formation induced by PAF. ASM and ceramide have relevance as a mediator of pulmonary edema and acute lung injury. Based on these findings, the inhibition of extracellular ASM and ceramide biosynthesis or action may serve as a new therapeutic strategy to treat pulmonary edema and other sequelae of inflammatory lung injuries.

References:

1.      Falk, S., Goggel, R., Heydasch, U., Brasch, F., Muller, K. M., Wendel, A., and Uhlig, S. Quinolines attenuate PAF-induced pulmonary pressor responses and edema formation. Am. J. Respir. Crit. Care Med. 160, 1734-1742 (1999).

2.      Goggel, R., Hoffman, S., Nusing, R., Narumiya, S., and Uhlig, S. Platelet-activating factor-induced pulmonary edema is partly mediated by prostaglandin E2, E-prostanoid 3-receptors, and potassium channels. Am. J. Respir. Crit. Care Med. 166, 657-662 (2002).