Abatement of bleomycin-induced pulmonary injury by cell-impermeable inhibitor of phospholipase A2 |
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| Institution: | 1. Pulmonary Research Laboratory, Institute of Pulmonology, Jerusalem 91120, Israel;2. Bone Marrow Transplantation Department, Hadassah University Hospital, Jerusalem 91120, Israel;3. Department of Biochemistry, Hebrew University Medical School, Jerusalem 91120, Israel;1. Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan;2. Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan;3. First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan;4. Division of Thoracic Surgery, Respiratory Disease Center, Seirei Mikatahara General Hospital, Hamamatsu, Japan;5. Department of Pathology, Seirei Mikatahara General Hospital, Hamamatsu, Japan;6. Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan;1. Department of Neurology, Changle People''s Hospital, Weifang, Shandong, China;2. Department of Geriatrics, Chengyang People’s Hospital, Qingdao, Shandong, China;3. Department of Geriatrics, Changle People''s Hospital, Weifang, Shandong, China;1. Center for Genetic Engineering and Biotechnology, P.O. Box. 6162, Habana 10600, Cuba;2. National Institute of Integral Agricultural Health (INSAI), Av. Principal Las Delicias. Edif. INIA, Maracay, Aragua, Venezuela |
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| Abstract: | The mechanism of bleomycin (Bleo)-induced pulmonary injury is not fully understood. Elevated levels of lung phospholipase A2 (PLA2) 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 cell impermeable inhibitor of PLA2 (CME) on Bleo-induced pulmonary inflammation in hamsters. Pulmonary injury was induced by a single IT instillation of Bleo (1 unit/0.5 ml saline). Three groups of male Syrian hamsters were evaluated: 1) BLEO-CME animals received IT Bleo and daily intraperitoneal (IP) injections of CME (1 μmole/kg), starting 1 day 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 treatment and lung injury was evaluated histologically by a semiquantitative morphologic index and by a differential cell count of bronchoalveolar lavage fluid. CME treatment significantly ameliorated Bleo-induced 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 group (P < 0.05), achieving levels comparable to SAL-SAL control animals. These results suggest that treatment with an extracellular PLA2 inhibitor-CME abates Bleo-induced pulmonary injury. This may indicate an active role of PLA2 in the pathogenesis of interstitial pulmonary fibrosis. |
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