Involvement of mannose receptor in glycopeptidolipid-mediated inhibition of phagosome-lysosome fusion.
We previously reported that glycopeptidolipid (GPL) isolated from Mycobacterium avium serovar 4 inhibited phagosome-lysosome (P-L) fusion when macrophages phagocytosed heat-killed Staphylococcus aureus (SA). In the present study we analyzed the underlying inhibitory mechanism of GPL coated on SA. Elimination of oligosaccharide from GPL abrogated its inhibitory activity. GPL did not inhibit P-L fusion of opsonized SA phagocytosed via complement receptors. The inhibitory activity of GPL was competitively reduced by the presence of alpha-methyl-D-mannoside and anti-mannose receptor antibody, suggesting that inhibition of P-L fusion by GPL is mediated through mannose receptor. Recruitment of early endosome antigen 1 and Ca2+/calmodulin kinase II in human macrophage-like THP-1 cells were significantly suppressed by GPL, indicating that GPL inhibits steps for leading to the P-L fusion.
Shimada
Ken-ichi
K
Department of Bioscience, School of Science, Kitasato University, Sagamihara, Kanagawa 228-8555, Japan.
Takimoto
Hiroaki
H
Yano
Ikuya
I
Kumazawa
Yoshio
Y
D002460:Cell Line; D006017:Glycolipids / Q000378:metabolism / Q000494:pharmacology*; D006020:Glycopeptides / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D008247:Lysosomes / Q000187:drug effects* / Q000502:physiology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D015269:Mycobacterium avium Complex / Q000472:pathogenicity*; D010587:Phagocytosis / Q000187:drug effects; D010588:Phagosomes / Q000187:drug effects* / Q000502:physiology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013211:Staphylococcus aureus
D006017:Glycolipids; D006020:Glycopeptides; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface