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

We have previously shown that mechanical distortion or stretch of alveolar type II (ATII) cells induces both surfactant release and the induction of a poptosis. We hypothesize that nitric oxide (NO) secreted from alveolar macr ophages (AMs) prevents cyclic stretch-induced apoptosis. We show that S-nit roso-N-acetyl-D,L-penicillamine (SNAP), a chemical donor of NO, protects ce lls 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 pr otective effect, and the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoli ne-1-oxyl 3-oxide blocked the antiapoptotic effect of SNAP. We also show th at AMs isolated from rat lung lavage fluid actively synthesize and secrete NO. Using a novel technique in which AMs were cocultured with ATII cells wh ile adhered to floating membrane rafts, we found that NO released from AMs was effective in protecting ATII cells from undergoing apoptosis. We theref ore propose that NO secreted by AMs may function as part of a physiological antiapoptotic mechanism that prevents ATII cells from undergoing stretch-i nduced cell death in the lung.