ACTIVATION OF POLYMORPHONUCLEAR LEUKOCYTES IN OLEIC ACID-INDUCED LUNGINJURY

Objective: Oleic acid (OA) can produce a lung injury similar to the ad ult respiratory dis tress syndrome (ARDS). Elastase and superoxides ar e thought to have an effect in ARDS. However, the effect that elastase and superoxide have in OA lung injury is unclear. To examine their in volvement in OA lung injury, we tested the effects of methoxysuccinyl- alanyl-alanyl-prolyl-valyl chloromethyl ketone (MAAPVCK), an elastase inhibitor, and N-acetyl-L-cysteine (NAC) an active oxygen scavenge;, o n the increase in pulmonary vascular permeability caused by OA. We als o examined whether OA stimulated elastase and/or superoxide release fr om polymorphonuclear leukocytes (PMNs). Design: Prospective trial. Set ting: University laboratory. Interventions: (1) Guinea pigs were anest hetized. MAAPVCK (2.5 mg/kg) or NAC (150 mg/kg) was infused over OA (1 5 mu l/kg) injection. Evans blue was used to measure vascular permeabi lity, (2) PMNs were isolated from the blood of guinea pigs and rats. E lastase release was measured with MeO-Suc-Ala-Ala-Pro-Val-7-amino-4-me thyl-coumarin. Superoxide production was measured by the ferricytochro me c reduction method. Measurements and results: OA caused pulmonary h emorrhage and an increase in vascular permeability. MAAPVCK and NAC si gnificantly attenuated the increase in vascular permeability in distal bronchus and trachea, respectively. OA induced superoxide production from PMNs in guinea pigs, but elastase release from PMNs was not detec ted. Conclusions: These results suggest that elastase and superoxide a re involved in OA lung injury.