Neutrophil elastase and oxygen radicals: Synergism in lung injury after hindlimb ischemia

C. R.B. Welbourn, G. Goldman, I. S. Paterson, C. R. Valeri, D. Shepro, H. B. Hechtman

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Hindlimb ischemia and reperfusion lead to lung injury dependent on activated polymorphonuclear neutrophils (PMN) adherence. This study tests whether elastase and oxygen radicals participate in PMN-induced injury once they have become sequestered in lungs. Anesthetized rats treated with saline (n = 9) or the specific elastase inhibitor methoxysuccinyl-L-Ala-L-Ala-L-Pro-L-Val-chloromethylketone (MAAPV, n = 6) underwent 4 h of bilateral hindlimb tourniquet ischemia followed by 4 h of reperfusion. At this time, in saline-treated rats, PMN were sequestered in lungs as assayed by myeloperoxidase activity [(MPO) 51 ± 5 U/g tissue], higher than MPO in saline-treated sham rats (n = 9; 18 ± 3 U/g MPO; P < 0.01); bronchoalveolar lavage (BAL) fluid leukotriene (LT) B4 levels increased to 594 ± 46 relative to 200 ± 38 pg/ml in shams (P < 0.01); increased permeability was documented by BAL fluid protein content of 599 ± 91 compared with 214 ± 35 μg/ml in sham animals (P < 0.01); and edema was shown by increase in lung wet-to-dry weight ratio of 4.77 ± 0.14 relative to 4.00 ± 0.09 in sham rats (P < 0.01). In MAAPV-treated animals, lung neutrophil sequestration (62 ± 9 U/g MPO) and rise of LTB4 in BAL fluid (780 ± 244 pg/ml) were not affected, but both BAL fluid protein (335 ± 32 μg/ml) and lung wet-to-dry weight ratio (4.21 ± 0.17) were reduced (both P < 0.05). Another group of rats (n = 7) was treated with the oxygen radical scavengers superoxide dismutase and catalase 2 h after removal of tourniquets. This did not affect lung neutrophil sequestration (58 ± 8 U MPO/g) but prevented the rise of LTB4 in BAL fluid (167 ± 44 pg/ml) as well as BAL fluid protein (245 ± 95 μg/ml) and lung wet-to-dry weight ratio (4.02±0.11) (all P<0.05). Infusion of MAAPV or oxygen radical scavengers into sham animals was without effect on neutrophil-endothelial interactions (23 ± 4 and 16 ± 1 U/g MPO, respectively). These data indicate that neutrophils sequestered in lungs after remote ischemia probably mediate permeability edema via release of both elastase and oxygen radicals.

Original languageEnglish
Pages (from-to)H1852-H1856
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number6 29-6
StatePublished - 1991
Externally publishedYes


  • Bronchoalveolar lavage
  • Leukotriene B
  • Neutrophil sequestration


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