title: Surfactant protein A (SP-A) mediates attachment of Mycobacterium tuberculosis to murine alveolar macrophages.
abstract: Attachment of Mycobacterium tuberculosis organisms to alveolar macrophages (AMs) is an essential early event in primary pulmonary tuberculosis. Surfactant protein A (SP-A) is a nonimmune opsonin present in the alveolar spaces that binds carbohydrate residues such as mannose. It was hypothesized that SP-A attaches to M. tuberculosis and serves as a ligand between M. tuberculosis and AMs. [125I]SP-A was found to bind to M. tuberculosis in a time- and [Ca2+]-dependent manner with a Kd of 1.9 x 10(-9) M and an apparent number of 6.3 x 10(2) SP-A binding sites/organism. Further, deglycosylated SP-A had minimal binding to M. tuberculosis, indicating that sugar moieties are important in this interaction. SP-A specifically binds to a 60-kD cell-wall protein from M. tuberculosis. SP-A-mediated attachment of 51Cr-labeled M. tuberculosis organisms to AMs is dependent on time, SP-A concentration, and Ca2+. M. tuberculosis attachment to murine AMs in the absence of SP-A was 12.8 +/- 0.9%; however, in the presence of 5 microg/ml SP-A the attachment increased to 38.6 +/- 2.9% (P < 0.001). SP-A-mediated attachment was significantly decreased from 38.6 +/- 2.9% to 18.7 +/- 3.3% (P < 0.05) in the presence of antihuman SP-A antibodies. When the attachment assay was repeated in the presence of alpha-methylene-D-mannosepyranosidase (mannosyl-BSA) and type V collagen, SP-A-mediated attachment decreased from 38.6 +/- 2.9% to 16.6 +/- 1.5% (P < 0.001) and 19.1 +/- 1.4% (P < 0.05), respectively. Further, deglycosylated SP-A had only a minimal effect on M. tuberculosis attachment to AMs. These data indicate that SP-A can mediate M. tuberculosis attachment to AMs, and suggest possible underlying mechanisms for this.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, USA.
authors.forename: R
authors.initials: R
authors.lastname: Pasula
authors.forename: J F
authors.initials: JF
authors.lastname: Downing
authors.forename: J R
authors.initials: JR
authors.lastname: Wright
authors.forename: D L
authors.initials: DL
authors.lastname: Kachel
authors.forename: T E
authors.initials: TE
authors.lastname: Davis
authors.forename: W J
authors.initials: WJ
authors.lastname: Martin
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology*; D007457:Iodine Radioisotopes; D016676:Macrophages, Alveolar / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D011510:Proteolipids / Q000502:physiology*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000502:physiology*; D051381:Rats
chemical_list: D007457:Iodine Radioisotopes; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants