ABATEMENT OF BLEOMYCIN-INDUCED PULMONARY INJURY BY CELL-IMPERMEABLE INHIBITOR OF PHOSPHOLIPASE-A2

The mechanism of bleomycin (Bleo)-induced pulmonary injury is not full y understood. Elevated levels of lung phospholipase A(2) (PLA(2)) have been previously reported following intratracheal (IT) instillation of Bleo, but the role of this enzyme in the pathogenesis of lung injury is not clear. In this pilot study, we have evaluated the effect of a c ell impermeable inhibitor of PLA(2) (CME) on Bleo-induced pulmonary in flammation in hamsters. Pulmonary injury was induced by a single IT in stillation of Bleo (1 unit/0.5 ml saline). Three groups of male Syrian hamsters were evaluated: 1) BLEO-CME animals received IT Bleo and dai ly intraperitoneal (IF) injections of CME (1 mu mole/kg), starting 1 d ay before IT instillation; 2) BLEO-SAL animals received IT Bleo and IP injections of saline and 3) SAL-SAL animals - treated with IT and IP administrations of saline. Animals were sacrificed 14 days after IT tr eatment and lung injury was evaluated histologically by a semiquantita tive morphologic index and by a differential cell count of bronchoalve olar lavage fluid. CME treatment significantly ameliorated Bleo-induce d lung injury compared to BLEO-SAL animals (P<0.05). The percentage of neutrophiles in bronchoalveolar lavage fluid was reduced from 17.7 +/ - 3.2% (mean +/-S.E.) in BLEO-SAL group to 7.3 +/- 1.7% in BLEO-CME gr oup (P < 0.05), achieving levels comparable to SAL-SAL control animals . These results suggest that treatment with an extracellular PLA(2) in hibitor-CME abates Bleo-induced pulmonary injury. This may indicate an active role of PLA(2) in the pathogenesis of interstitial pulmonary f ibrosis.