NO protects alveolar type II cells from stretch-induced apoptosis. A novel role for macrophages in the lung

被引:30
作者
Edwards, YS [1 ]
Sutherland, LM [1 ]
Murray, AW [1 ]
机构
[1] Flinders Univ S Australia, Fac Sci & Engn, Sch Biol Sci, Adelaide, SA 5001, Australia
关键词
apoptotic stimuli; antiapoptotic factors; mechanical distortion; S-nitroso-N-acetyl-D; L-penicillamine; sorbitol-induced osmotic shock;
D O I
10.1152/ajplung.2000.279.6.L1236
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
We have previously shown that mechanical distortion or stretch of alveolar type II (ATII) cells induces both surfactant release and the induction of apoptosis. We hypothesize that nitric oxide (NO) secreted from alveolar macrophages (AMs) prevents cyclic stretch-induced apoptosis. We show that S-nitroso-N-acetyl-D,L-penicillamine (SNAP), a chemical donor of NO, protects cells against nuclear condensation and DNA fragmentation induced by stretch (30% at 60 cycles/min) as well as by sorbitol. SNAP depleted of NO had no protective effect, and the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide blocked the antiapoptotic effect of SNAP. We also show that AMs isolated from rat lung lavage fluid actively synthesize and secrete NO. Using a novel technique in which AMs were cocultured with ATII cells while adhered to floating membrane rafts, we found that NO released from AMs was effective in protecting ATII cells from undergoing apoptosis. We therefore propose that NO secreted by AMs may function as part of a physiological antiapoptotic mechanism that prevents ATII cells from undergoing stretch-induced cell death in the lung.
引用
收藏
页码:L1236 / L1242
页数:7
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