SP-A enhances uptake of bacillus Calmette-Guérin by macrophages through a specific SP-A receptor

• Published in: The American journal of physiology Vol. 272; no. 5 Pt 1; p. L989
• Main Authors: Weikert, L F, Edwards, K, Chroneos, Z C, Hager, C, Hoffman, L, Shepherd, V L
• Format: Journal Article
• Language: English
• Published: United States 01.05.1997
• Subjects: Animals; Bone Marrow Cells; Female; Humans; Macrophages - physiology; Macrophages, Alveolar - physiology; Monocytes - physiology; Mycobacterium bovis - metabolism; Mycobacterium bovis - physiology; Phagocytosis; Proteolipids - metabolism; Proteolipids - pharmacology; Pulmonary Surfactant-Associated Protein A; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants - metabolism; Pulmonary Surfactants - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Cell Surface - physiology
• ISSN: 0002-9513
• DOI: 10.1152/ajplung.1997.272.5.L989

Surfactant-associated protein A (SP-A) is a C-type lectin that is involved in surfactant metabolism as well as host defense functions in the lung. We have recently identified a receptor on macrophages [specific 210-kDa SP-A receptor (SPR210)] that binds SP-A. In the current study we have investigated the role of SP-A in mediating uptake of bacillus Calmette-Guérin (BCG) by rat macrophages and human monocytes and have examined the role of the macrophage SPR210 in this process. 125I-labeled SP-A bound BCG in a Ca(2+)-, carbohydrate-, and dose-dependent manner. To examine association of SP-A-BCG complexes with macrophages, BCG were opsonized with SP-A and were incubated with rat bone marrow-derived macrophages (RBMM), rat alveolar macrophages (RAM), or human monocytes at a 1-to-1 ratio for 4 h. The cells were washed, fixed in formalin, and stained with auramine-rhodamine. Cell-associated organisms were enumerated by fluorescent microscopy. The percentage of cells with one or more associated BCG was increased by SP-A from 27% of RBMM with BCG alone to 54% with SP-A-BCG complexes; 1-16% in RAM; and 39-67% in human monocytes. This enhanced uptake was dependent on the dose of SP-A, with maximal increases seen with 10 micrograms/ml. Electron microscopic analysis supported the conclusion that organisms were ingested by and not simply bound to the macrophages. Inclusion of SPR210 antibodies blocked association of SP-A-BCG complexes, suggesting a role for SPR210 in mediating the interaction of SP-A-BCG with the macrophages. This was further supported by the finding that modulation of SPR210 activity resulted in altered SP-A-BCG uptake. These results demonstrate that SP-A binds to BCG and that uptake of these SP-A-BCG complexes is mediated in part by the SPR210 on rat macrophages and human monocytes.