ROLES OF PHOSPHOLIPASE A_2 IN MULTIPLE ORGAN DYSFUNCTION SYNDROME

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*1*Phospholipase A_2 (PLA_2) has been postulated as a key mediator in the development of adult respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODF) following severe trauma, hemorrhagic shock and severe infection. Our clinical research syggested that serum type II PLA_2 increased markedly in the patients of critical illness.*2*Hypoperfusion to the gut has been suggested to cause MODF following severe trauma and hemorrhagic shock. The study using RI angiography showed that disproportionate intestinal hypoperfusion persisted for a long period even after blood pressure recovered.*3*We have developed a gut ischemia-reperfusion (I/R) rat model and found that superior mesenteric artery clamp and declamp induces lung injury by a PLA_2-dependent mechanism. The subtype analysis revealed that the most part of PLA_2 existing in the ischemic gut was secretory type II.Furthermore, the pretreatment with type II PLA_2 inhibitor, S-5920, blocked gut I/R-induced lung injury.*4*These findings suggest that type II PLA_2 plays an impirtant role in the development of ARDS and MODF after severe teauma, hemorrhagic shock and severe infection. Type II PLA_2 inhibitor may become am useful drug for prevention and treatmnt of ARDS and MODS in critically injured patients.