Lipophosphoglycan from Leishmania mexicana promastigotes binds to members of the CR3, p150,95 and LFA-1 family of leukocyte integrins.
The abundant surface glycolipid, promastigote lipophosphoglycan (LPG), of Leishmania promastigotes was isolated and reconstituted onto the surface of hydrophobic silica beads. These beads bound to both macrophages and monocytes, suggesting that phagocytes possess a receptor(s) capable of recognizing LPG. LPG beads were unable to bind to macrophages isolated from individuals with a genetic deficiency in the CD18 complex of leukocyte integrins (CR3, p150,95, and LFA-1), suggesting that one or more of these receptors were required for binding of LPG. Individual members of the CD18 complex were depleted from macrophages by plating cells on surfaces coated with anti-receptor mAb. These experiments indicated that CR3 and p150,95 from the CD18 complex, were the predominant mediators of attachment of LPG. The phagocyte receptor CR3 expresses two distinct binding sites, one that binds peptide ligands, such as C3bi, and a second site, that recognizes bacterial LPS. Antibody inhibition experiments and competition binding studies with synthetic peptides and soluble LPG indicated that LPG is recognized by the nonpeptide, or "LPS" binding site on CR3.
Talamás-Rohana
P
P
Department of Pathology, NYU Medical Center, NY 10016.
Wright
S D
SD
Lennartz
M R
MR
Russell
D G
DG
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001665:Binding Sites; D018821:CD18 Antigens; D006028:Glycosphingolipids / Q000378:metabolism*; D006801:Humans; D007158:Immunologic Techniques; D066298:In Vitro Techniques; D016167:Integrin alphaXbeta2; D016023:Integrins / Q000378:metabolism*; D007894:Leishmania mexicana / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1; D008264:Macrophages / Q000469:parasitology*; D009000:Monocytes / Q000469:parasitology*; D011951:Receptors, Complement / Q000378:metabolism; D016028:Receptors, Leukocyte-Adhesion / Q000378:metabolism*
D000943:Antigens, Differentiation; D018821:CD18 Antigens; D006028:Glycosphingolipids; D016167:Integrin alphaXbeta2; D016023:Integrins; D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1; D011951:Receptors, Complement; D016028:Receptors, Leukocyte-Adhesion; C008290:lipophosphonoglycan