Am. J. Respir. Crit. Care Med., Volume 156, Number 5, November 1997, 1679-1687

Effects of Proteinosis Surfactant Proteins on the Viability of Rat Alveolar Macrophages

HUI-QING SHEN, CHEN-XIA DUAN, ZHONG-YUAN LI, and YASUHIRO SUZUKI

Department of Molecular Pathology, Chest Disease Research Institute, Kyoto University, Kyoto, Japan

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.

This article has been cited by other articles:

				M. A. Ryan, H. T. Akinbi, A. G. Serrano, J. Perez-Gil, H. Wu, F. X. McCormack, and T. E. Weaver Antimicrobial Activity of Native and Synthetic Surfactant Protein B Peptides J. Immunol., January 1, 2006; 176(1): 416 - 425. [Abstract] [Full Text] [PDF]

				F. Brasch, J. Birzele, M. Ochs, S.H. Guttentag, O.D. Schoch, A. Boehler, M.F. Beers, K.M. Muller, S. Hawgood, and G. Johnen Surfactant proteins in pulmonary alveolar proteinosis in adults Eur. Respir. J., September 1, 2004; 24(3): 426 - 435. [Abstract] [Full Text] [PDF]

				F. Brasch, M. Griese, M. Tredano, G. Johnen, M. Ochs, C. Rieger, S. Mulugeta, K.M. Muller, M. Bahuau, and M.F. Beers Interstitial lung disease in a baby with a de novo mutation in the SFTPC gene Eur. Respir. J., July 1, 2004; 24(1): 30 - 39. [Abstract] [Full Text] [PDF]

				K. Tashiro, K. Ohta, X. Cui, K. Nishizuka, K. Yamamoto, T. Konzaki, T. Kobayashi, and Y. Suzuki Effects of various forms of surfactant protein C on tidal volume in ventilated immature newborn rabbits J Appl Physiol, April 1, 2003; 94(4): 1519 - 1526. [Abstract] [Full Text] [PDF]

				J. F. Seymour and J. J. Presneill Pulmonary Alveolar Proteinosis: Progress in the First 44 Years Am. J. Respir. Crit. Care Med., July 15, 2002; 166(2): 215 - 235. [Abstract] [Full Text] [PDF]