en
Scientific article
English

Integration of mycobacterial lipoarabinomannans into glycosylphosphatidylinositol-rich domains of lymphomonocytic cell plasma membranes

Published inThe Journal of immunology, vol. 155, no. 3, p. 1334-1342
Publication date1995
Abstract

Lipoarabinomannans (LAMs) are major Ags of the mycobacterial cell envelope where they apparently insert through a glycosylphosphatidylinositol (GPI) anchoring structure. LAMs induce host macrophages to secrete TNF-alpha, IL-1, and IL-6 and inhibit T cell proliferative responses. The mechanisms by which LAMs mediate these effects remain poorly understood. We show that LAMs were efficiently inserted into the plasma membranes of human and murine lymphomonocytic cells through their GPI anchor. Prior deacylation of LAMs abrogated this event. Phosphatidylinositol hexamannoside (PIM6), the GPI anchor of all LAMs, competitively inhibited LAM insertion. Deacylated PIM6 was not inhibitory. The hexamannoside glycan of PIM6 appears to be important for LAM insertion, since phosphatidylinositol from soybean, lacking the glycan core, was not as efficient an inhibitor. Interaction of LAM with target cells was influenced by the gel/fluid phase distribution of membrane lipids, suggesting a direct interaction of the LAM-GPI anchor with the membrane bilayer. The inserted LAMs were mobile in the plane of the membrane and interfered with Ab-mediated mobilization of the GPI-anchored Thy-1 molecules. Further, LAMs were preferentially incorporated into isolated plasma membrane vesicles enriched in Thy-1. Our results strongly suggest that 1) interaction of LAMs with host lymphomonocytic cells is mediated through a preferential integration of LAM-GPI anchor into specialized plasma membrane domains enriched in endogenous GPI-anchored molecules, and 2) both the acyl chains and the mannoside core glycan of the LAM-GPI anchor contribute to the specificity of integration.

Keywords
  • Acylation
  • Animals
  • Antigens, Bacterial/ metabolism
  • Cell Membrane/ metabolism
  • Flow Cytometry
  • Glycosylphosphatidylinositols/ metabolism
  • Humans
  • Kinetics
  • Lipopolysaccharides/ metabolism
  • Lymphocytes/ metabolism/ultrastructure
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Confocal
  • Mycobacterium/ metabolism
  • Mycobacterium tuberculosis/metabolism
  • Phosphatidylinositols/ metabolism
  • Tumor Cells, Cultured
Affiliation Not a UNIGE publication
Citation (ISO format)
ILANGUMARAN, Subburaj et al. Integration of mycobacterial lipoarabinomannans into glycosylphosphatidylinositol-rich domains of lymphomonocytic cell plasma membranes. In: The Journal of immunology, 1995, vol. 155, n° 3, p. 1334–1342.
Main files (1)
Article
accessLevelRestricted
Identifiers
ISSN of the journal0022-1767
465views
0downloads

Technical informations

Creation08/27/2010 1:34:50 PM
First validation08/27/2010 1:34:50 PM
Update time03/14/2023 4:03:40 PM
Status update03/14/2023 4:03:40 PM
Last indexation02/12/2024 7:18:21 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack