Induction of inflammatory mediators in human airway epithelial cells by lipid ozonation products

We have proposed that exposure of epithelial cell membrane lipids in the lu ng (mainly phospholipids) to ozone will generate lipid ozonation products ( LOP), which could be responsible for the proinflammatory effects of ozone. The ozonation of phosphocholine, the principal membrane phospholipid, produ ces a limited number of LOP, including hydroxyhydroperoxides and aldehydes. We now report that exposure of cultured human bronchial epithelial cells t o the ozonized 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) prod uct, 1-palmitoyl-2-(9-oxononanoyl)-sn-glycero-3-phosphocholine (PC-ALD), a phospholipase A(2) (PLA(2))-stimulatory LOP, resulted in a 113 +/- 11% incr ease in the amounts of tritiated platelet-activating factor (H-3-PAF) relea sed apically. H-3-PAF release was also induced by 1-hydroxy-1-hydroperoxyno nane of ozonized POPC (HHP-C9), a phospholipase C (PLC)stimulatory LOP (134 +/- 40% increase in H-3-PAF). PC-ALD at 10 mu M, but not HHP-C9, induced a 127 +/- 24% increase in prostaglandin E-2 (PGE(2)) release (n = 6, p < 0.0 5). In contrast, HHP-C9, but not PC-ALD, induced interleukin (IL)-6 release (178 +/- 23% increase, n = 6, p < 0.05) and IL-8 release (101 +/- 23% incr ease, n = 8,p < 0.05). These results suggest that LOP-dependent release of proinflammatory mediators may play an important role in the early inflammat ory response seen during exposure to ozone.