SPONTANEOUS HEAT-SHOCK PROTEIN-SYNTHESIS BY ALVEOLAR MACROPHAGES IN INTERSTITIAL LUNG-DISEASE ASSOCIATED WITH PHAGOCYTOSIS OF EOSINOPHILS

Synthesis of heat shock proteins (HSPs) is induced in all cells and ti ssues after exposure to elevated temperatures, or a variety of other t ypes of injury, including oxidative injury. We have previously reporte d that stress proteins are induced in monocytes-macrophages during pha gocytosis of red blood cells. Receptor-mediated phagocytosis is associ ated with activation of the respiratory burst, generation of the lipid mediators of inflammation, and increased production of cytokines. Sim ilar activation events have been described in the alveolar macrophage (AM) during pulmonary fibrosis. We therefore analysed the pattern of p roteins synthesized by human AMs recovered by bronchoalveolar lavage ( BAL) in interstitial lung disease, both under basal conditions and aft er in vitro exposure to heat or hydrogen peroxide (H2O2). In two out o f the 17 cases studied, we observed a high alveolar eosinophilia (10 a nd 24%, respectively) and phagocytosis, by the AMs, of eosinophilic ma terial. Whereas exposure to heat or H2O2 induced in all AMs the synthe sis of the classical HSPs, in these two cases, we found spontaneous sy nthesis of HSPs and of a 32 kD oxidation-specific stress protein, haem e oxygenase (HO). Exposure of AM to purified eosinophil-derived protei ns, such as major basic protein (MBP), eosinophil peroxidase (EPO), eo sinophil-derived neurotoxin (EDN), alone or in combination, did not in duce stress protein synthesis, further suggesting that phagocytosis is involved in this induction. Stress protein synthesis by AMs may repre sent a new cellular marker of pulmonary injury and eosinophilic inflam mation, and an autoprotective mechanism against oxidative stress.