Effects of glucose-regulated protein94 (Grp94) on Ig secretion from human blood mononuclear cells

Elisa Tramentozzi, Rita Zamarchi, Andrea Pagetta, Anna Maria Brunati, Elisabetta Rossi, Elena Tibaldi, Paola Finotti

Research output: Contribution to journalArticlepeer-review

Abstract

Grp94 is the main endoplasmic reticulum-resident heat shock protein (HSP) that besides chaperoning native proteins, displays important modulatory effects on both the innate and adaptive immune response. Since the knowledge of a direct influence of Grp94 on the humoral response is lacking, in this work we tested the effect of Grp94 on Ig secretion from peripheral blood mononuclear cells (PBMCs) of five normal volunteers. The concentration of Ig secreted in the medium after incubation of 15 days was found increased in a dose-dependent manner in the presence of Grp94, used at the final concentrations of 10 and 100 ng/ml. However, by measuring the Ig secretion at different incubation times, it was apparent that maximal percent stimulation by Grp94 occurred at 7 days, decreasing thereafter. In addition, the pattern of Ig secretion in time significantly differed in the presence of Grp94 with respect to that of control PBMCs. Grp94 also stimulated in a dose-dependent manner the PBMC proliferation, an effect that preceded the Ig secretion and was accompanied by morphological changes of cells similar to those induced by the pokeweed mitogen. Effects of Grp94 on PBMCs were mediated by an intense activation of the MEK-ERK1/2 pathway and by an increased expression of HSP90. Results indicate that Grp94 can activate the humoral response by a cytokine-like, cell-mediated mechanism that leads to an accelerated process of B cell maturation and differentiation.

Original languageEnglish
Pages (from-to)329-338
Number of pages10
JournalCell Stress and Chaperones
Volume16
Issue number3
DOIs
Publication statusPublished - May 2011

Keywords

  • Antibody production
  • Cell proliferation
  • Extracellular signal-regulated MAP kinases
  • Heat shock proteins
  • Lymphocyte activation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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