LUNG SURFACTANT: A Personal Perspective

Abstract

This perspective tells the story of the discovery, characterization, and understanding of the surfactant system of the lung; of how investigators from many disciplines studied the system, stimulated by the demonstration of surfactant deficiency in respiratory distress syndrome of the newborn; and of how the resulting knowledge formed a basis for highly successful surfactant substitution treatment for this syndrome. The chapter includes personal reminiscences and reflections of the author and ends with a few thoughts about the present status and future prospects of this field of research. PrologueWhen the editor of the Annual Review of Physiology invited me to write a perspective on lung surfactant, I had serious misgivings. I had just finished preparing a historical chapter on the subject for the American Physiological Society's series People and Ideas (18), and I was also a bit concerned about intruding my own story. I decided finally to write a perspective that would include information and commentary on the development of the field and some autobiographical material. This chapter is not intended to be prefatory to other chapters on respiratory physiology in this volume. Because the People and Ideas chapter treated the background and early history of the field at length, this one covers those aspects in less detail. Discovery of Lung Surfactant and Its Clinical SignificanceFor over a century, students of physiology were taught that breathing consists of an alternating balance between the force of the respiratory muscles and the elastic recoil of the chest wall and lung tissue. During quiet breathing, the 1 0066-4278/97/0315-0001$08.00 Annu. Rev. Physiol. 1997.59:1-21 As it happened, I was serving my two years of military duty as a medical officer at the Medical Laboratories, and one of my assignments was to monitor the Harvard contract. That may sound like a dull job, but it turned out to be pure joy. The research was so fine, and Jere Mead was such a wonderful, enthusiastic, open kind of scientist, that I was in heaven discussing the work with him and his colleagues. Here was I, a neophyte in respiratory physiology, admitted into the inner council of leaders in the field. I knew their thinking long before it was published, and it was they who first aroused my interest in the problem of surface tension in the pulmonary alveoli. Before I could understand it, though, I had to study some fundamental concepts, such as the nature of surface tension, the operation of surfactants, and the meaning of Laplace's relationship.Surface tension is the tendency of a liquid surface to contract due to the cohesive forces between the molecules in and near the surface. These forces are enormous, about 13 orders of magnitude greater than the force of the earth's gravity on the molecules. Unlike gravity, which acts over huge distances, cohesive forces are significant only between molecules that are almost touching. The stronger the attractive forces, the greater the tendency of the surface to shrink. If the system permits ...

F-actin scaffold stabilizes lamellar bodies during surfactant secretion

“…Lamellar bodies (LBs) are vesicles that store surfactant phospholipids in complex with surfactant proteins B (SPB) and C (5). Physiological stimuli such as lung hyperinflation induce surfactant secretion, which occurs by LB exocytosis (1,11).…”

Hyaluronan Decreases Surfactant Inactivation In Vitro

“…Over the past decade, pulmonary surfactant replacement has revolutionized the therapy of respiratory distress syndrome of premature infants (1)(2)(3). However, effects of surfactant therapy are less dramatic when used to treat lung diseases associated with acute lung injury and acute respiratory distress syndrome (4 -7).…”

Increased pulmonary blood flow does not alter surfactant protein gene expression in lambs within the first week of life

“…In children with congenital heart disease with increased pulmonary blood flow, the changes in SP expression may play a significant role in the aberration in lung compliance (15,16) and increased susceptibility to pulmonary infection (18) seen in this pathological state. The function of surfactant, a complex lipoprotein assembled and secreted in the alveolar space by type II cells, is to lower surface tension at the air-water interface of the lung alveoli, thereby stabilizing lung volume at low transpulmonary pressures.…”