Surfactant Protein A and D Differently Regulate the Immune Response to NonmucoidPseudomonas aeruginosaand Its Lipopolysaccharide

Abstract

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-alpha 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.

Aggregation ofCryptococcus neoformansby Surfactant Protein D Is Inhibited by Its Capsular Component Glucuronoxylomannan

“…It is thought that an important function of this protein is to aggregate microorganisms, thereby facilitating their mucociliary clearance (9). SP-D can also enhance uptake and killing by phagocytic cells (4,24,29). However, depending on the pathogen involved, in some cases SP-D binding to microorganisms impairs their subsequent uptake by phagocytes (13,39).…”

“…Coupling of FITC was stopped by addition of excess NH 4 Cl, and unincorporated label was removed by gel filtration chromatography by using Bio-Gel P-10 (Bio-Rad) in a spin column.…”

“…Binding of microorganisms by SP-D can result in their aggregation (22,25,27), which is thought to stimulate their removal by enhancing their mucociliary clearance (9). Furthermore, binding of SP-D to microorganisms can stimulate (4,24,29) as well as inhibit (13,39) their subsequent uptake and killing by phagocytes, depending on the specific pathogen involved.…”

Innate Immune Collectin Surfactant Protein D Simultaneously Binds Both Neutrophil Extracellular Traps and Carbohydrate Ligands and Promotes Bacterial Trapping

“…Because SP-D binds to NETs as well as microbes, we next asked whether SP-D could alter bacterial trapping by NETs. To answer this question, we first tested whether SP-D can bind to our laboratory strain of P. aeruginosa, mPAO1 (46). We incubated P. aeruginosa or E. coli with SP-D (5 mg/ml) for various time periods and monitored the changes in absorbance at 600 nm.…”

Surfactant Protein D Is Present in Human Tear Fluid and the Cornea and Inhibits Epithelial Cell Invasion byPseudomonas aeruginosa

“…has been associated with microbial aggregation, inhibition of microbial growth, complement activation, stimulation of macrophage cytokine production, and the enhancement of microbial phagocytosis by immune cells (5,21,29,33,39). However, these antimicrobial effects vary between different microbial genera, species, or strains.…”