[The damaging effect of activated human neutrophils on isolated perfused rat lungs--the role of elastase].
Human neutrophil and its elastase play an important role in the pathogenesis of various lung diseases. We investigated the damaging effect of human neutrophils stimulated with PMA (phorbol myristate acetate 10ng/ml) or calcium ionophase A23187 (2ng/ml) on isolated perfused rat lungs. The study specimens consisted of 4 groups of animals. A control, B perfused with human neutrophils, C perfused with human neutrophils stimulated with PMA, and D perfused with human neutrophils stimulated with A23187. By using the ELISA method, we found that the level of human neutrophil elastase (HNE) in perfusate increased significantly at 30min (1.68 +/- 0.79ng/ml P < 0.05) and 60min (2.35 +/- 0.87 ng/ml P < 0.01) after PMA stimulating, but the HNE in the lung lavage fluid of the same group only slightly increased and the concentration of protein in lavage fluid did not change. After stimulating with A23187, the concentration of HNE in perfusate increased markedly at 30min (4.03 +/- 1.96ng/ml P < 0.01) and maintained at high level (P < 0.01). There was a significant increase of HNE level in lung lavage fluid (2.49 +/- 0.61ng/ml) from group D rat lungs, compared with group A, B or C, and the protein as well (1.61 +/- 0.58mg/ml P < 0.05). All the results indicate that the stimulated human neutrophils can release elastase in perfused rat lung. Neutrophil stimulated with A23187 can increase pulmonary permeability and injure the lung. We suggest that the lung damage, caused by human neutrophils, may be the effect of neutrophil elastase or the synergistic effect with some other substances derived from neutrophil.
Guo
Z
Z
PUMC Hospital, CAMS, Beijing.
Zhu
Y
Y
Yan
Y
Y
Xi
P
P
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D066298:In Vitro Techniques; D019272:Leukocyte Elastase / Q000502:physiology*; D008168:Lung / Q000473:pathology*; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000502:physiology*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000001:Calcimycin; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D013755:Tetradecanoylphorbol Acetate