Alveolar type II cells isolated after silica-induced lung injury in rats have increased surfactant protein A (SP-A) receptor activity.
We examined surfactant secretion and its regulation by surfactant protein A (SP-A) in alveolar type II cells isolated from silica-treated rats to determine the role of SP-A-mediated regulatory control of phospholipid secretion in the pathogenesis of silica-induced alveolar proteinosis. Type II cells were isolated at weekly intervals for 28 d after silica or saline instillation. The maximum total binding of [125I]SP-A (internalized and surface-bound SP-A) to type II cells increased with time after silica instillation and, at 21 d, was 4-fold greater than that of type II cells isolated from saline-treated rats (272.8 +/- 42.5 and 65.4 +/- 9.8 ng/10(5) cells, respectively; P less than 0.05). Type II cells isolated from silica-treated rats showed a 2-fold increased surface binding and a 3-fold increased internalization compared to control cells. The receptor affinity for SP-A was the same for type II cells isolated from silica- and saline-treated animals. Type II cells isolated 14 d after silica instillation were separated into normotrophic and hypertrophic populations by centrifugal elutriation. Hypertrophic cells showed significantly elevated maximum total binding compared to normotrophic cells. The secretion of [3H]phosphatidylcholine [( 3H]PC) by type II cells from silica- and saline-treated animals was also compared. Type II cells from silica-treated animals showed lower basal and tetradecanoyl phorbol acetate (TPA)-stimulated [3H]PC secretion than cells from saline-treated animals at each time point after instillation. SP-A inhibited TPA-stimulated [3H]PC secretion similarly in type II cells isolated after either silica or saline instillation.(ABSTRACT TRUNCATED AT 250 WORDS)
Suwabe
A
A
Lord and Taylor Laboratory for Lung Biochemistry, Department of Medicine, National Jewish Center for Immunology, Respiratory Medicine, Denver, Colorado 80206.
Panos
R J
RJ
Voelker
D R
DR
D000818:Animals; D010743:Phospholipids / Q000378:metabolism; D011510:Proteolipids / Q000378:metabolism*; D011649:Pulmonary Alveolar Proteinosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000473:pathology; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012822:Silicon Dioxide / Q000633:toxicity*
D010743:Phospholipids; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D011956:Receptors, Cell Surface; C067774:surfactant protein A receptor; D012822:Silicon Dioxide