Pathology of the surfactant system of the mature lung.

Abstract

At a symposium titled Pathology of the-Surfactant System of the Mature Lung, held in March 1995 in San Diego, California, researchers from such diverse fields as molecular and cellular biology, pulmonary biology, neonatology, and immunology dis­ cussed recent developments in the field of surfactant biology. Topics of discussion included the function of surfactant proteins, biosynthesis and function of surfactant phospholipids, host defenses, and both preclinical and clinical studies with novel sur­ factant preparations. THE FUNCTION6F SURFACTANT APOPROTEINS The various surfactant proteins (SP) are distinctly different in structure and function. Samuel Hawgood, M.D., Ph.D., provided new evidence regarding how these apoproteins interact in vivo to influence surfactant intracellular assembly, structure, and func­ tion. Using monoclonal antibodies that specifically recognize ei­ ther mature dirneric 18 kD S~B or the 43 kD SP-B precursor, Dr. Hawgood demonstrated that only SP-B precursors exist in the Golgi apparatus and endoplasmic reticulum of the type II cell, while only mature SP-B exists in lamellar bodies; both forms exist in multivesicular and composite bodies. He suggested that the intracellular processing and maturation of SP-B is impor­ tant for the maturation and packing of lipids. This suggestion is supported by experiments showing that SP-B functions as a powerful fusigen, causing lipid vesicles to associate 0, 2). In studies of the structure of SP-A, Dr. Hawgood identified three calcium binding sites and presented data suggesting that calcium binding induces a structural change in SP-A that facili­ tates interaction of SP-A with lipid or SP-B. Thus, he speculated that exposure of SP-A to calcium is the trigger that transforms the lamellar body to tubular myelin in the extracellular space. Although electron microscopic study of these structures revealed no morphologic changes with the addition of SP-C, addition of SP-C in vivo caused a dramatic improvement in function. Only when all three apoproteins were present in surfactant prepara­ tions added to the lung of a premature rabbit was function pre­ served in the presence of plasma proteins. In contrast to SP-A and SP-B, relatively less is known about the function of SP-C. The mature molecule contains a series of cysteine residues in the amino terminal region to which palmi