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Surfactant Protein A and D Differently Regulate the Immune Response to Nonmucoid Pseudomonas aeruginosa and Its Lipopolysaccharide

Dr. von Haunersches Kinderspital, University of Munich, Munich, Germany; Department of Pathology, Washington University, School of Medicine, St. Louis, Missouri; and Max von Pettenkofer Institut, University of Munich, Munich, Germany

Address correspondence to: Matthias Griese, Dr. von Haunersches Kinderspital, University of Munich, Pettenkoferstrasse 8a, D-80336 Munich, Germany. E-mail: griese{at}pk-i.med.uni-muenchen.de

We investigated the role of the surfactant proteins (SPs) A and D in the pulmonary immune defense of nonmucoid strains of Pseudomonas aeruginosa, the most etiologic agents of nosocomial Pseudomonas pneumonia. We first examined the interactions of recombinant human SP-D dodecamers and purified natural or recombinant human SP-A with two smooth, and two rough, clinical isolates of nonmucoid P. aeruginosa. SP-D bound to all four isolates, but agglutinated only one rough and one smooth strain. SP-D functioned as an opsonin to enhance the uptake of all four strains by the human monocytic cell line Mono Mac 6 (MM6). SP-D also enhanced tumor necrosis factor- secretion by MM6 cells in response to purified lipopolysaccharide (LPS) isolated from the rough, but not the smooth, strains. Although SP-A bound to all four strains, it did not cause bacterial aggregation or enhance uptake. It showed small but statistically significant inhibitory effects on the cytokine response of MM6 cells to one strain of smooth organisms, but did not significantly alter the response to purified LPS. This study in combination with previously published data strongly suggests that SP-D may play important roles in the local innate pulmonary defense against nonmucoid P. aeruginosa of diverse LPS phenotypes, and preferentially augments the cellular response to rough P. aeruginosa endotoxin.

Abbreviations: colony-forming units, cfu • ethylenediamine tetraacetic acid, EDTA • fetal calf serum, FCS • fluorescein isothiocyanate, FITC • lipopolysaccharide, LPS • Mono Mac 6, MM6 • phosphate-buffered saline, PBS • surfactant protein, SP • Tris-buffered saline, TBS • tumor necrosis factor, TNF

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