Alterations of surfactant lipid turnover in silicosis: evidence of a role for surfactant-associated protein A (SP-A).
Type II cell hypertrophy with surfactant accumulation in the lung is a common observation in silicosis. Mechanisms leading to these alterations are poorly understood. By using silica dusts and alveolar fluids from saline and silica exposed sheep, we explored four different pathways of surfactant turnover in vitro: (1) synthesis and (2) secretion of lipids by rat type II cells; and dipalmitoylphosphatidylcholine (DPPC) uptake/reuptake by (3) type II cells and (4) alveolar macrophages. Silica had no direct specific effect on type II cell lipid metabolism. Alveolar fluids from both saline and silica exposed animals induced several alterations compared to control medium: (a) an increase in lipid synthesis (60 to 130%, P < 0.05); (b) a decrease in lipid secretion (25 to 70%, P < 0.05); (c) a 50 to 75% increase in DPPC reuptake by type II cells (P < 0.05); (d) a 65 to 75% decrease in DPPC uptake by alveolar macrophages (P < 0.05). DPPC uptake by in vivo silica exposed alveolar macrophages was reduced. Alterations of surfactant lipid metabolism induced by alveolar fluids from silicotic animals was more pronounced than in those treated with control fluids. Anti SP-A antibodies significantly suppressed most of the alveolar fluid induced effects on surfactant turnover. From these in vitro data, silica-induced type II cell hypertrophy seems to result from an increase in lipid synthesis activity and an imbalance in the lipid secretion/reuptake ratio.
Lesur
O
O
Unité de Recherche Pulmonaire, Université de Sherbrooke, Québec, Canada.
Bouhadiba
T
T
Melloni
B
B
Cantin
A
A
Whitsett
J A
JA
Bégin
R
R
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D000818:Animals; D001059:Apoproteins / Q000502:physiology*; D002478:Cells, Cultured; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism* / Q000502:physiology*; D012756:Sheep; D012829:Silicosis / Q000378:metabolism*
D001059:Apoproteins; D010743:Phospholipids; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; C046616:pulmonary surfactant apoprotein; D015060:1,2-Dipalmitoylphosphatidylcholine