Phenolic glycolipid-1 of Mycobacterium leprae binds complement component C3 in serum and mediates phagocytosis by human monocytes.
Previous studies from this laboratory have demonstrated that Mycobacterium leprae, an obligate intracellular bacterial parasite, enters human mononuclear phagocytes via complement receptors on these host cells and bacterium-bound C3. The present study investigates the role of M. leprae surface molecules in C3 fixation and phagocytosis. By enzyme-linked immunosorbent assay, C3 binds selectively to phenolic glycolipid-1 (PGL-1), a major surface molecule of the leprosy bacillus. C3 fixation to PGL-1 is serum concentration dependent and is abolished in heat-inactivated serum or serum containing ethylenediaminetetraacetic acid. C3 fixation is also abolished in serum containing ethyleneglycol-bis (beta-aminoethyl ether)N,N,N'-tetraacetic acid and MgCl2 indicating that isolated PGL-1 fixes C3 via the classical complement pathway. The capacity of PGL-1 to fix C3 is dependent upon its terminal trisaccharide since sequential removal of monosaccharide units of the trisaccharide results in a stepwise reduction in C3 fixation. Deacylation of PGL-1 also abolishes C3 fixation. C3 fixes to the trisaccharide of PGL-1 that is chemically linked to bovine serum albumin via the chemical carrier, 8-methoxycarbonyloctanol. PGL-1 mediates C3 fixation to polystyrene microspheres, and PGL-1 and C3 together mediate ingestion of polystyrene microspheres by human monocytes, wherein these inert test particles reside in membrane-bound phagosomes. Thus, complement receptors on mononuclear phagocytes, complement component C3, and PGL-1 comprise a three-component receptor-ligand-acceptor molecule system for mediating phagocytosis of M. leprae.
Department of Medicine, UCLA School of Medicine 90024.
L S
LS
Schlesinger
M A
MA
Horwitz
D000942:Antigens, Bacterial / Q000502:physiology*; D003167:Complement Activation; D003176:Complement C3 / Q000502:physiology*; D006017:Glycolipids / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D009000:Monocytes / Q000276:immunology*; D009166:Mycobacterium leprae / Q000276:immunology*; D010587:Phagocytosis / Q000502:physiology*; D011951:Receptors, Complement / Q000502:physiology
D000942:Antigens, Bacterial; D003176:Complement C3; D006017:Glycolipids; D011951:Receptors, Complement; C045169:phenolic glycolipid I, Mycobacterium leprae