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 tissues after exposure to elevated temperatures, or a variety of other types of injury, including oxidative injury. We have previously reported that stress proteins are induced in monocytes-macrophages during phagocytosis of red blood cells. Receptor-mediated phagocytosis is associated with activation of the respiratory burst, generation of the lipid mediators of inflammation, and increased production of cytokines. Similar activation events have been described in the alveolar macrophage (AM) during pulmonary fibrosis. We therefore analysed the pattern of proteins synthesized by human AMs recovered by bronchoalveolar lavage (BAL) in interstitial lung disease, both under basal conditions and after in vitro exposure to heat or hydrogen peroxide (H2O2). In two out of the 17 cases studied, we observed a high alveolar eosinophilia (10 and 24%, respectively) and phagocytosis, by the AMs, of eosinophilic material. Whereas exposure to heat or H2O2 induced in all AMs the synthesis of the classical HSPs, in these two cases, we found spontaneous synthesis of HSPs and of a 32 kD oxidation-specific stress protein, haeme oxygenase (HO). Exposure of AM to purified eosinophil-derived proteins, such as major basic protein (MBP), eosinophil peroxidase (EPO), eosinophil-derived neurotoxin (EDN), alone or in combination, did not induce stress protein synthesis, further suggesting that phagocytosis is involved in this induction. Stress protein synthesis by AMs may represent a new cellular marker of pulmonary injury and eosinophilic inflammation, and an autoprotective mechanism against oxidative stress.
Allergy Unit, University Hospital, Geneva, Switzerland.
B S
BS
Polla
S
S
Kantengwa
G J
GJ
Gleich
M
M
Kondo
C M
CM
Reimert
A F
AF
Junod
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004591:Electrophoresis, Polyacrylamide Gel; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis; D006801:Humans; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010587:Phagocytosis / Q000502:physiology*; D011657:Pulmonary Eosinophilia / Q000276:immunology*; D011658:Pulmonary Fibrosis / Q000276:immunology / Q000378:metabolism*; D016897:Respiratory Burst / Q000502:physiology
D006360:Heat-Shock Proteins; D006419:Heme Oxygenase (Decyclizing)