Effects of proteinosis surfactant proteins on the viability of rat alveolar macrophages.
Pulmonary alveolar proteinosis (PAP) is a disease of unknown etiology that is characterized by the accumulation of protein- and lipid-rich insoluble material in alveoli and terminal bronchioles of the lung. Alveolar macrophages (AM) in PAP are reportedly extremely large and have low viability. We investigated substances in lavaged lung material from patients with PAP that induced these cellular changes in rat AM. Rat AM were incubated for various periods with liposomes prepared from lipids and isolated hydrophobic surfactant apoproteins, and cell size, viability, and lactate dehydrogenase release were determined. Of the hydrophobic apoproteins, a dimeric form of surfactant-associated protein-C ([SP-C]2) had the most marked effects. In addition, [SP-C]2 induced increased superoxide anion release at an early phase (6 to 12 h) and an increase in glutathione content at 24 h of incubation. At 3 d after incubation, cellular glutathione and adenosine triphosphate (ATP) content were significantly decreased in cells treated with [SP-C]2, [SP-C]2 was presumed to cause early cell death through increased formation of superoxide anion and the subsequent derangement of cellular metabolism. [SP-C]2 was not removed from cells, and SP-B and SP-C were removed at slower rates than lipids. The changes in macrophages induced by [SP-C]2 may contribute to establishing PAP.
Shen
H Q
HQ
Department of Molecular Pathology, Chest Disease Research Institute, Kyoto University, Japan.
Duan
C X
CX
Li
Z Y
ZY
Suzuki
Y
Y
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001059:Apoproteins / Q000494:pharmacology / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D048429:Cell Size; D002470:Cell Survival; D002478:Cells, Cultured; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008081:Liposomes; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000502:physiology*; D008297:Male; D011510:Proteolipids / Q000494:pharmacology / Q000502:physiology; D011649:Pulmonary Alveolar Proteinosis / Q000503:physiopathology*; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism
D001059:Apoproteins; D008054:Lipid Peroxides; D008081:Liposomes; D011510:Proteolipids; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; C046616:pulmonary surfactant apoprotein; D013481:Superoxides; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D005978:Glutathione