title: SP-A enhances uptake of bacillus Calmette-Guérin by macrophages through a specific SP-A receptor.
abstract: 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.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: L F
authors.initials: LF
authors.lastname: Weikert
authors.forename: K
authors.initials: K
authors.lastname: Edwards
authors.forename: Z C
authors.initials: ZC
authors.lastname: Chroneos
authors.forename: C
authors.initials: C
authors.lastname: Hager
authors.forename: L
authors.initials: L
authors.lastname: Hoffman
authors.forename: V L
authors.initials: VL
authors.lastname: Shepherd
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D005260:Female; D006801:Humans; D008264:Macrophages / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000502:physiology; D009000:Monocytes / Q000502:physiology; D009163:Mycobacterium bovis / Q000378:metabolism / Q000502:physiology*; D010587:Phagocytosis; D011510:Proteolipids / Q000378:metabolism / Q000494:pharmacology*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000502:physiology*
chemical_list: D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D011956:Receptors, Cell Surface; C067774:surfactant protein A receptor