Surfactant protein D enhances phagocytosis and killing of unencapsulated phase variants of Klebsiella pneumoniae.
Pulmonary surfactant protein D (SP-D) is a collagenous C-type lectin (collectin) that is secreted into the alveoli and distal airways of the lung. We have studied the interactions of SP-D and alveolar macrophages with Klebsiella pneumoniae, a common cause of nosocomial pneumonia. SP-D does not agglutinate encapsulated K. pneumoniae but selectively agglutinates spontaneous, unencapsulated phase variants, such as Klebsiella strain K50-3OF, through interactions with their lipopolysaccharides (LPS). These effects are calcium dependent and inhibited with maltose but not lactose, consistent with involvement of the SP-D carbohydrate recognition domain. Precoating of K50-3OF with SP-D enhances the phagocytosis and killing of these organisms by rat alveolar macrophages in cell culture and stimulates the production of nitric oxide by the NR-8383 rat alveolar macrophage cell line. SP-D similarly enhances the NO response to K50-3OF LPS adsorbed to Latex beads under conditions where soluble LPS or SP-D, or soluble complexes of SP-D and LPS, do not stimulate NO production. Our studies demonstrate that interactions of SP-D with exposed arrays of Klebsiella LPS on a particulate surface can enhance the host defense activities of alveolar macrophages and suggest that activation of macrophages by SP-D requires binding to microorganisms or other particulate ligands. Because unencapsulated phase variants are likely to be responsible for the initial stages of tissue invasion and infection, we speculate that SP-D-mediated agglutination and/or opsonization of K. pneumoniae is an important defense mechanism for this respiratory pathogen in otherwise healthy individuals.
Ofek
I
I
Department of Human Microbiology, Tel Aviv University, Tel Aviv, Israel.
Mesika
A
A
Kalina
M
M
Keisari
Y
Y
Podschun
R
R
Sahly
H
H
Chang
D
D
McGregor
D
D
Crouch
E
E
D000371:Agglutination; D000818:Animals; D006023:Glycoproteins / Q000378:metabolism / Q000494:pharmacology*; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis; D010587:Phagocytosis / Q000187:drug effects*; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats
D006023:Glycoproteins; D008070:Lipopolysaccharides; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D009569:Nitric Oxide