Highlights of Early Pulmonary Surfactant: Research from Bench to Clinic
More details
Hide details
Center for Host Defense, Inflammation, and Lung Disease CHILD Research Department of Pediatrics, The Pennsylvania State University, Hershey, Pennsylvania, USA
Department of Obstetrics and Gynecology, College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania, USA
Corresponding author
Joanna Floros   

Department of Pediatrics 500 University Drive MC H085 Hershey, Pennsylvania 17033 USA,
Pneumon 2013;26(4):350-354
Nowadays we know a great deal about the lung. We understand its major functions, how it achieves most of these, how it looks microscopically, and other physiological attributes such as that adequate amounts of pulmonary surfactant in the prematurely born infant are essential for lung function and consequently for life. In this review, we summarize highlights of the history, i.e. the journey of pulmonary surfactant discovery and how it moved from the lab bench to the patient’s bedside.
FDA= Food and Drug Administration, NIH= National Institutes of Health, DPPC= dipalmitoyl phosphatidylcholine, SP-= surfactant proteins, BAL= bronchoalveolar lavage, RDS= respiratory distress syndrome, SP-A= surfactant protein A, AMs= alveolar macrophages, UTR= untranslated region
This work was supported by the NIH HL34788 grant.
No conflicts of interest, financial or otherwise are declared by the author(s).
Fujiwara T, Robertson B. Pharmacology of exogenous surfactant. In B. Robertson, L. M. G. Van Golde, and J. J. Batenburg, editors: Elsevier, Amsterdam; 1992:561–92.
Griese M, Dietrich P, Reinhardt D. Pharmacokinetics of bovine surfactant in neonatal respiratory distress syndrome. Am J Respir Crit Care Med 1995;152:1050-4.
Wiseman LR, Bryson HM. Porcine-derived lung surfactant. A review of the therapeutic efficacy and clinical tolerability of a natural surfactant preparation (Curosurf) in neonatal respiratory distress syndrome. Drugs 1994;48:386-403.
Ainsworth SB, Beresford MW, Milligan DW, et al. Pumactant and poractant alfa for treatment of respiratory distress syndrome in neonates born at 25-29 weeks’ gestation: a randomised trial. Lancet 2000;355:1387-92.
Wrobel S. Bubbles, Babies and Biology: The Story of Surfactant. FASEB J 2004;18:1624e-.
K. NV. Neue auffassungen uber einen grundbegriff der atemmechanik. Die retraktionskraft der lunge, abhangig von der oberflachenspannung in den alveolen. Z Gesamt Exp Med1929:373–94.
Gruenwald P. Surface tension as a factor in the resistance of neonatal lungs to aeration. Am J Obstet Gynecol 1947;53:996- 1007.
Pattle RE. Properties, function and origin of the alveolar lining layer. Nature 1955;175:1125-6.
Pattle RE. Properties, function, and origin of the alveolar lining layer. Proc R Soc Lond B Biol Sci 1958;148:217-40.
Clements J. Dependence of pressure-volume characteristics of lungs on intrinsic surface active material. Am J Physiol1956:592.
Clements JA. Surface tension of lung extracts. Proc Soc Exp Biol Med 1957;95:170-2.
Macklin CC. The pulmonary alveolar mucoid film and the pneumonocytes. Lancet 1954;266:1099-104.
Avery ME, Mead J. Surface properties in relation to atelectasis and hyaline membrane disease. AMA J Dis Child 1959;97:517- 23.
Enhörning G, Robertson B. Expansion patterns in the premature rabbit after tracheal deposition of surfactant. Acta Pathol Microbiol Scand A 1971;79:682.
Enhörning G, Robertson B. Lung expansion in the premature rabbit fetus after tracheal deposition of surfactant. Pediatrics 1972;50:58-66.
King RJ, Clements JA. Surface active materials from dog lung. I. Method of isolation. Am J Physiol 1972;223:707-14.
King RJ, Clements JA. Surface active materials from dog lung. II. Composition and physiological correlations. Am J Physiol 1972;223:715-26.
King RJ, Clements JA. Surface active materials from dog lung. 3. Thermal analysis. Am J Physiol 1972;223:727-33.
Harwood JL. Lung surfactant. Biochem Soc Trans 1987;15 Suppl:80S-9S.
Adams FH, Towers B, Osher AB, Ikegami M, Fujiwara T, Nozaki M. Effects of tracheal instillation of natural surfactant in premature lambs. I. Clinical and autopsy findings. Pediatr Res 1978;12:841-8.
Robillard E, Alarie Y, Dagenais-Perusse P, Baril E, Guilbeault A. Microaerosol administration of synthetic beta-gamma-dipalmitoyl-L-alpha-lecithin in the respiratory distress syndrome. A preliminary report. Can Med Assoc J 1964;90:55-7.
Fujiwara T, Maeta H, Chida S, Morita T, Watabe Y, Abe T. Artificial surfactant therapy in hyaline-membrane disease. Lancet 1980;1:55-9.
Halliday HL. Overview of clinical trials comparing natural and synthetic surfactants. Biol Neonate 1995;67 Suppl 1:32-47.
Halliday HL. Surfactants: past, present and future. J Perinatol 2008;28 Suppl 1:S47-56.
Robertson B CT, Johansson J, Jornvall H, Kobayashi T. Structural and functional characterization of porcine surfactant isolated by liquid-gel chromatography. Prog Resp Res1990:237–46.
Phelps DS. Surfactant regulation of host defense function in the lung: a question of balance. Pediatr Pathol Mol Med 2001;20:269-92.
Floros J, Phelps DS. Pulmonary surfactant protein A; structure, expression, and its role in innate host defense. In: Nakos G, Lekka ME, eds. Surfactant-Update of Intensive Care Medicine. Ioannina, Greece: University of Ioannina; 2002:87-102.
Wright JR. Immunomodulatory functions of surfactant. Physiol Rev 1997;77:931-62.
Griese M. Pulmonary surfactant in health and human lung diseases: state of the art. Eur Respir J 1999;13:1455-76.
Frerking I, Günther A, Seeger W, Pison U. Pulmonary surfactant: functions, abnormalities and therapeutic options. Intensive Care Med 2001;27:1699-717.
Crouch EC. Collectins and pulmonary host defense. Am J Respir Cell Mol Biol 1998;19:177-201.
Floros J, Phelps DS. Pulmonary surfactant. In: Biebuck J, Lynch Iii C, Maze M, Saidman LJ, Yaksh TL, Zapol WM, eds. Anesthesia: Biologic Foundations: Lippincott-Raven; 1997:1259-79.
Wang G, Bates-Kenney SR, Tao JQ, Phelps DS, Floros J. Differences in biochemical properties and in biological function between human SP-A1 and SP-A2 variants, and the impact of ozone-induced oxidation. Biochemistry 2004;43:4227-39.
Floros J, Thomas N. Genetic variations of surfactant proteins and lung injury. Nakos G, and Papathanasiou A, editors. Surfactant Pathogenesis and Treatment of Lung Diasease2009:25-48.
Silveyra P, Wang G, Floros J. Human SP-A1 (SFTPA1) variant-specific 3’ UTRs and poly(A) tail differentially affect the in vitro translation of a reporter gene. Am J Physiol Lung Cell Mol Physiol 2010;299:L523-34.
Silveyra P, Raval M, Simmons B, Diangelo S, Wang G, Floros J. The untranslated exon B of human surfactant protein A2 mRNAs is an enhancer for transcription and translation. Am J Physiol Lung Cell Mol Physiol 2011;301:L795-803.
Wang G, Guo X, Floros J. Differences in the translation efficiency and mRNA stability mediated by 5’-UTR splice variants of human SP-A1 and SP-A2 genes. Am J Physiol Lung Cell Mol Physiol 2005;289:L497-508.
Noutsios GT, Silveyra P, Bhatti F, Floros J. Exon B of human surfactant protein A2 mRNA, alone or within its surrounding sequences, interacts with 14-3-3; role of cis-elements and secondary structure. Am J Physiol Lung Cell Mol Physiol 2013;304:L722-35.
Wang G, Myers C, Mikerov A, Floros J. Effect of cysteine 85 on biochemical properties and biological function of human surfactant protein A variants. Biochemistry 2007;46:8425-35.
Huang W, Wang G, Phelps DS, Al-Mondhiry H, Floros J. Human SP-A genetic variants and bleomycin-induced cytokine production by THP-1 cells: effect of ozone-induced SP-A oxidation. Am J Physiol Lung Cell Mol Physiol 2004;286:L546-53.
Wang G, Umstead T, Phelps D, Al-Mondhiry H, Floros J. The effect of ozone exposure on the ability of human surfactant protein a variants to stimulate cytokine production. Environ Health Perspect 2002;110:79-84.
Mikerov AN, Umstead TM, Huang W, Liu W, Phelps D, Floros J. SP-A1 and SP-A2 variants differentially enhance association of Pseudomonas aeruginosa with rat alveolar macrophages. Am J Physiol Lung Cell Mol Physiol 2005;288:L150-L8.
Mikerov A, Wang G, Umstead T, et al. Surfactant protein A2 (SPA2) variants expressed in CHO cells stimulate phagocytosis of Pseudomonas aeruginosa more than do SP-A1 variants. Infect Immun 2007;75:1403-12.
Mikerov AN, Umstead TM, Gan X, et al. Impact of ozone exposure on the phagocytic activity of human surfactant protein A (SP-A) and SP-A variants. Am J Physiol Lung Cell Mol Physiol 2008;294:L121-30.
Wang G, Guo X, Diangelo S, Thomas NJ, Floros J. Humanized SFTPA1 and SFTPA2 transgenic mice reveal functional divergence of SP-A1 and SP-A2: formation of tubular myelin in vivo requires both gene products. J Biol Chem 2010;285:11998-2010.
Tagaram HR, Wang G, Umstead TM, et al. Characterization of a human surfactant protein A1 (SP-A1) gene-specific antibody; SP-A1 content variation among individuals of varying age and pulmonary health. Am J Physiol Lung Cell Mol Physiol 2007;292:L1052-63.
Wang Y, Voelker DR, Lugogo NL, et al. Surfactant protein A is defective in abrogating inflammation in asthma. Am J Physiol Lung Cell Mol Physiol 2011;301:L598-606.
Bersani I, Speer CP, Kunzmann S. Surfactant proteins A and D in pulmonary diseases of preterm infants. Expert Rev Anti Infect Ther 2012;10:573-84.
Phelps DS, Umstead TM, Quintero OA, Yengo CM, Floros J. In vivo rescue of alveolar macrophages from SP-A knockout mice with exogenous SP-A nearly restores a wild type intracellular proteome; actin involvement. Proteome Sci 2011;9:67.
Silveyra P, Floros J. Air pollution and epigenetics: effects on SP-A and innate host defence in the lung. Swiss Med Wkly 2012;142:w13579.
Journals System - logo
Scroll to top