Surfactant protein A prevents silica-mediated toxicity to rat alveolar macrophages.
Silicosis is a serious occupational lung disease associated with irreversible pulmonary fibrosis. The interaction between inhaled crystalline silica and the alveolar macrophage (AM) is thought to be a key event in the development of silicosis and fibrosis. Silica can cause direct injury to AMs and can induce AMs to release various inflammatory mediators. Acute silicosis is also characterized by a marked elevation in surfactant apoprotein A (SP-A); however, the role of SP-A in silicosis is unknown. We investigated whether SP-A directly affects the response of AMs to silica. In this study, the degree of silica toxicity to cultured rat AMs as assessed by a (51)Cr cytotoxicity assay was shown to be dependent on the time of exposure and the concentration and size of the silica particles. Silica directly injured rat AMs as evidenced by a cytotoxic index of 32.9 +/- 2.5, whereas the addition of rat SP-A (5 microg/ml) significantly reduced the cytotoxic index to 16.6 +/- 1.2 (P < 0. 001). This effect was reversed when SP-A was incubated with either polyclonal rabbit anti-rat SP-A antibody or D-mannose. These data indicate that SP-A mitigates the effect of silica on AM viability, and this effect may involve the carbohydrate recognition domain of SP-A. The elevation of SP-A in acute silicosis may serve as a normal host response to prevent lung cell injury after exposure to silica.
Spech
R W
RW
Division of Pulmonary, Allergy, Critical Care, and Occupational Medicine, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Wisniowski
P
P
Kachel
D L
DL
Wright
J R
JR
Martin
W J
WJ
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D016676:Macrophages, Alveolar / Q000187:drug effects*; D008358:Mannose / Q000494:pharmacology; D009994:Osmolar Concentration; D011510:Proteolipids / Q000276:immunology / Q000494:pharmacology*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000276:immunology / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000037:antagonists & inhibitors* / Q000506:poisoning*; D013997:Time Factors
D000906:Antibodies; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012822:Silicon Dioxide; D008358:Mannose