PMID: 7536932Apr 11, 1995Paper

Activation of Ca2+ signaling in neutrophils by the mast cell-released immunophilin FKBP12

Proceedings of the National Academy of Sciences of the United States of America
H BangD Swandulla

Abstract

The immunophilins of the FK506-binding protein (FKBP) family are intracellular proteins that bind the immunosuppresants FK506 and rapamycin. In this study we show that HMC-1 mast cells sensitized with IgE release FKBP12 upon stimulation with anti-IgE. The release is rapid and not affected by actinomycin D or cycloheximide, suggesting that it is due to exocytosis from a storage compartment. FKBP12 from HMC-1 mast cells exhibits biological activity. When applied extracellularly to human neutrophils, it induces transient changes in the intracellular Ca2+ concentration ([Ca2+]i) due to Ca2+ release from intracellular stores. Inhibition of [Ca2+]i changes by ruthenium red and ryanodine indicates that ryanodine receptor/Ca2+ release channels are involved in FKBP12-induced Ca2+ signaling. Neutrophil activation by mast cell-derived FKBP12 is prevented by complexing FKBP12 with FK506 or rapamycin. These results demonstrate that extracellular FKBP12 functions as a cytokine in cell-to-cell communication. They further suggest a pathophysiological role for FKBP12 as a mediator in immediate or type I hypersensitivity and may have implications for novel therapeutic strategies in the treatment of allergic disorders with FK506 and rapamycin.

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Citations

Mar 26, 1999·European Journal of Immunology·W SchorrH U Zeilhofer
Dec 26, 2008·Journal of Biomolecular Structure & Dynamics·Alexander M Andrianov
Apr 29, 2000·Current Opinion in Hematology·H U Zeilhofer, W Schorr
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Dec 3, 2014·Immunology Letters·Pulak Ranjan Nath, Noah Isakov
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Sep 30, 2003·Rapid Communications in Mass Spectrometry : RCM·Annika DahlAnn Westman-Brinkmalm
Dec 19, 1998·Journal of Medicinal Chemistry·G S Hamilton, J P Steiner

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