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 (colle ctin) that is secreted into the alveoli and distal airways of the lung. We have studied the interactions of SP-D and alveolar macrophages with Klebsie lla pneumoniae, a common cause of nosocomial pneumonia. SP-D does not agglu tinate 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 calciu m dependent and inhibited with maltose but not lactose, consistent with inv olvement 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 nitri c oxide by the NR-8383 rat alveolar macrophage cell line. SP-D similarly en hances the NO response to K50-3OF LPS adsorbed to Latex beads under conditi ons 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 activ ation of macrophages by SP-D requires binding to microorganisms or other pa rticulate ligands. Because unencapsulated phase variants are likely to be r esponsible for the initial stages of tissue invasion and infection, we spec ulate that SP-D-mediated agglutination and/or opsonization of K. pneumoniae is an important defense mechanism for this respiratory pathogen in otherwi se healthy individuals.