R. Breuer et al., ABATEMENT OF BLEOMYCIN-INDUCED PULMONARY INJURY BY CELL-IMPERMEABLE INHIBITOR OF PHOSPHOLIPASE-A2, Life sciences, 57(16), 1995, pp. 237-240
Citations number
10
Categorie Soggetti
Biology,"Medicine, Research & Experimental","Pharmacology & Pharmacy
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.