A role for lipid rafts in C1q-triggered O2- generation by human neutrophils

Iyore Otabor, Shivraj Tyagi, Frank J.M. Beurskens, Ionita Ghiran, Pascale Schwab, Anne Nicholson-Weller, Lloyd B. Klickstein

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Calreticulin, a candidate C1q receptor, was shown recently to be present on the surface of human neutrophils in association with glycosylphosphatidylinositol (GPI) anchored proteins, particularly CD59. In this study, we show that antibodies to CD59, as well as to every other GPI-anchored protein tested, inhibited the C1q-triggered release of O2- from PMN. Methyl β cyclodextrin (MβCD) treatment of the cells to disrupt lipid rafts also prevented C1q-triggered O2- production. β2 integrin-dependent co-stimulation is required for O2- production from PMN, however MβCD had no effect on LFA-1 or Mac-1-mediated adhesion, soluble iC3b binding to PMN, or spreading and migration, all of which suggested that PMN integrin function remained intact. Flow cytometric analysis of PMN treated with MβCD showed upregulation of PMN granule-associated integrins and a corresponding increase in integrin activation-reporter epitopes, in contrast to the decreased expression of GPI-anchored antigens. These data support a model where lipid rafts and their associated GPI-anchored proteins are critical for C1q-triggered O 2- production, consistent with a model where calreticulin serves as the C1q receptor for O2- production from PMN.

Original languageEnglish (US)
Pages (from-to)185-190
Number of pages6
JournalMolecular Immunology
Volume41
Issue number2-3
DOIs
StatePublished - Jun 1 2004

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Keywords

  • GPI
  • LFA-1
  • Mac-1
  • Methyl-β-cyclodextrin
  • MβCD
  • O
  • PMN
  • complement receptor 3 or CD11b/CD18
  • glycosylphosphatidylinositol
  • leukocyte function antigen-1 or CD11a/CD18
  • polymorphonuclear leukocyte or neutrophil
  • superoxide

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

Cite this

Otabor, I., Tyagi, S., Beurskens, F. J. M., Ghiran, I., Schwab, P., Nicholson-Weller, A., & Klickstein, L. B. (2004). A role for lipid rafts in C1q-triggered O2- generation by human neutrophils. Molecular Immunology, 41(2-3), 185-190. https://doi.org/10.1016/j.molimm.2004.03.029