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.

The incidence of tuberculosis is increasing on a global scale, in part due to its strong association with human immunodeficiency virus (HIV) infection. Attachment of Mycobacterium tuberculosis to its host cell, the alveolar macrophage (AM), is an important early step in the pathogenesis of infection. Bronchoalveolar lavage of HIV-infected individuals demonstrated the presence of a factor which significantly enhances the attachment of tubercle bacilli to AMs 3-fold relative to a normal control population. This factor is surfactant protein A (SP-A). SP-A levels are increased in the lungs of HIV-infected individuals. SP-A levels and attachment of M. tuberculosis to AMs inversely correlate with peripheral blood CD4 lymphocyte counts. Elevated concentrations of SP-A during the progression of HIV infection may represent an important nonimmune risk factor for acquiring tuberculosis, even before significant depletion of CD4 lymphocytes in the peripheral blood occurs.