The interaction of a lung surfactant protein (SP-A) with macrophages is mannose dependent.
Lung surfactant protein A (SP-A) is the main protein component of pulmonary surfactant, which lines the alveolar space. We examined the interaction between recombinant human SP-A and human macrophages or monocytes. Binding and uptake of SP-A adsorbed onto colloidal gold particles was followed by electron microscopy and quantitated on micrographs. SP-A particles were internalized via coated pits/vesicles and transported to secondary lysosomes. Uptake was inhibited in the presence of alpha-D-mannosyl-bovine serum albumin (BSA) but not by beta-D-galactosyl-BSA. Two mannose-dependent recognition mechanisms might mediate SP-A uptake by macrophages. First, as SP-A is a glycoprotein with N-glycosylated glycans it could act as a ligand for the mannose-specific receptor on macrophages. Second, as SP-A is a mannose-specific lectin itself it could bind to mannose residues on the macrophage's cell surface. Activity of the Man-receptor on macrophages was demonstrated with alpha-D-mannosyl-BSA coated onto gold particles. Exposed alpha-D-mannosyl residues on macrophages were identified by Concanavalin A adsorbed onto gold particles. Hence, both mechanisms may be involved in principle. As monocytes have no mannose-specific receptor activity on their cell surface but internalize SP-A gold particles in a mannose-dependent manner, we conclude that at least the second mechanism participates in the recognition of SP-A by macrophages.
Wintergerst
E
E
Faculty of Biology, University of Konstanz, Federal Republic of Germany.
Manz-Keinke
H
H
Plattner
H
H
Schlepper-Schäfer
J
J
D004705:Endocytosis; D006651:Histocytochemistry; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000648:ultrastructure; D008358:Mannose / Q000494:pharmacology*; D008855:Microscopy, Electron, Scanning; D009000:Monocytes / Q000378:metabolism / Q000648:ultrastructure; D011510:Proteolipids / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D008358:Mannose