Lipoglycans are putative ligands for the human pulmonary surfactant protein A attachment to mycobacteria. Critical role of the lipids for lectin-carbohydrate recognition.
The human pulmonary surfactant protein A (hSP-A) has been implicated in the early capture and phagocytosis of the pathogenic Mycobacterium tuberculosis by alveolar macrophages. In this report, we examined the interaction of alveolar proteinosis patient hSP-A with Mycobacterium bovis BCG, the vaccinating strain, as a model of pathogenic mycobacteria, and Mycobacterium smegmatis, a nonpathogenic strain. We found that hSP-A binds to the surface of M. bovis BCG, but also to a slightly lesser extent, to M. smegmatis, indicating that hSP-A does not discriminate between virulent and nonpathogenic strains. Among the various glycoconjugates isolated from the mycobacterial envelope, we found that the best ligands are the two major lipoglycans: the mannosylated lipoarabinomannan (ManLAM) and the lipomannan. In contrast, the mannose-capped arabinomannan, structurally close to the ManLAM, as well as the LAMs from the non pathogenic M. smegmatis are poorly recognized by hSP-A. These results clearly show that the presence of both the terminal mannose residues and the phophatidyl-myo-inositol anchor are necessary to achieve the highest binding affinity. Selective removal of either the terminal mannose or the acyl residues esterifying the glycerol moiety of the ManLAM abrogates the interaction with hSP-A, further supporting the notion that the hSP-A recognition of the carbohydrate epitopes of the lipoglycans is dependent of the presence of the fatty acids.
Sidobre
S
S
Institut de Pharmacologie et de Biologie Structurale du CNRS, 205 route de Narbonne, 31077 Toulouse Cedex, France.
Nigou
J
J
Puzo
G
G
Rivière
M
M
D002236:Carbohydrate Conformation; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D008024:Ligands; D050356:Lipid Metabolism; D008070:Lipopolysaccharides / Q000737:chemistry / Q000378:metabolism*; D009161:Mycobacterium / Q000378:metabolism* / Q000472:pathogenicity; D011510:Proteolipids / Q000378:metabolism*; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism*
D037102:Lectins; D008024:Ligands; D008070:Lipopolysaccharides; D011510:Proteolipids; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants