| The effect of superoxide anion production by PMN on pneumocyte injury in patients with bronchial asthma. |
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Young Kyoon Kim, Sung Hak Park |
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Department of Internal Medicine, Catholic University Medical College, Seoul, Korea |
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| Abstract |
Background
Bronchial asthma has been known as an in f1 mmatory disease. There have been man y evidences that polymorphonuc1 ear leukocytes (PMN) might play an irnportant role in the pathogrnesis of asthma. Although many investigators suggested that pneumocyte injury by PMN .derived oxygen radicals may contribute to the pathogenesis of asthma, there has been few report for a direct evidence of oxygen radicals.mediated pneumocyte injury in bronchial asthma. Furthermore the exact mechanism of oxygen radicals mediated pneumocyte injury is still controversy . This study was designed to establish a direct in vitro evidence and its c1 inical significance of pneumocyte injury by PMN .derived superoxide anion in bronchial asthma and to elucidate the main mechanism of superox. ide anion.mediated pneumocyte injury.
Methods
12 stable asthmatics and 5 healthy volunteers were participated in this study . PMN was separated from peripheral venous blood samples by using dextran sedimentation and Ficoll.H ypaque densit y gradient separation method. Superox ide anion productions by PMN and plasma SOD activities were measured by spectrophotometric assay using the principle of SOD inhibitable cytochrom e c reduction . PMN .mediated pneumocyte injuries were measured by 5l Cr.release assay using A549 pneumocytes and were expressed as percent lysis and percent detachment.
Results
1) PMN from asthmatics produced more amount of superoxide anion compared to PMN fr om normal subjects (6.65 ::t 0.58 vs 2.81 ::t 0.95 nmol / 1 x 106 cells, p < 0. 05), and showed an inverse correla.
tion with FEV1 (R= - 0.63 , p < 0 . 05), but no correlation with PC20 histamine in asthmatics.
2) Plasma SOD activities were decreased in asthmatics compared to normal subjects but not significant , and showed a positive correlation with FEV1 (R=0.63, p < 0.05) but no correlation with PC20 histamine in asthmatics.
3) There were a positive correlation between plasma SOD activity and superoxide anion production by PMN in normal subjects (R=0.88, p < 0.05) but not in asthmatics.
4) PMN-mediated pneumocyte injury was predominantly expressed as cell detachment rather than cell lysis in both groups, and PMN from asthmatics showed more potent cytotoxic effect on A549 pneumocytes compated to PMN from normal subjects. PMN .mediated detachment rather than lysis of A549 pneumocytes was significantly inhibited by in vitro SOD but not by diluted serum.
5) PMN .mediated detachment rather than lysis of A549 pneumocytes showed a good correlation with superoxide anion production by PMN (R = 0.90 in normal subjects, R= 0.82 in asthmatics, p < 0.05) but no correlation with plasma SOD activity . PMN .mediated pneumocyte injuries were not correlated with FEV1 or PC20 histamine in asthmatics.
6) There were no significant differences in PMN .mediated pneumocyte injuries between allergic and nonallergic asthmatics.
Conclusion
Our results suggest that pneumocyte injury by PMN -derived superoxide anion may partially contribute to the pathogenesis of asthma and that cell detachment rather than cell lysis may be the mechanism of superoxide anion-mediated pneumocyte injury. |
| Key Words:
PMN, Superoxide, Pneumocyte injury, Asthma |
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