Extracellular ATP activates mast cells via a mechanism that is different from the activation induced by the cross-linking of Fc receptors

Nobuyuki Sudo, Kazuo Tanaka, Yasuhiro Koga, Yuushi Okumura, Chiharu Kubo, Kikuo Nomoto

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42 Citations (Scopus)

Abstract

In this study, the extracellular ATP (ATPo)-induced biochemical events were elucidated by comparing them with either the FcεRI- or FcγR-induced events in the mouse mast cell line MC9. The omission of extracellular Ca2+ almost completely abolished the elevation of intracellular Ca2+ ([Ca2+](i)) in the ATPo-stimulated cells, but only suppressed the second phase of the increase of [Ca2+](i) in FcR-stimulated cells, thus suggesting that the ATPo-induced elevation of [Ca2+](i) is totally dependent on the entry of extracellular Ca2+. Pretreatment with genistein, which inhibits protein kinases, especially protein tyrosine kinase, inhibited the FcR- triggered increase of [Ca2+2+](i), but not the ATPo-triggered one; however, such pretreatment did suppress both ATPo- and FcR-mediated β-hexosaminidase release. An immunoblot analysis revealed that both ATPo and the cross- linking of FcRs led to tyrosine phosphorylation of 44- and 110-kDa proteins, which thus suggested that these tyrosine-phosphorylated proteins are involved in a modulation of the degranulation process following an elevation of [Ca2+](i). Pretreatment with PMA inhibited the FcR-induced [Ca2+](i) increase, while not inhibiting the ATPo-induced one, thus suggesting that ATPo can mobilize [Ca2+](i) even when protein kinase C (PKC) has already been activated. Pretreatment of calphostin C, a specific PKC inhibitor, had little effect on the ATPo-mediated β-hexosaminidase secretion, thus indicating that the ATPo-induced degranulation is not mediated by PKC. Taken together, these results demonstrate that ATPo activates MC9 mast cells by a mechanism that is different from the activation induced by the cross-linking of FcRs.

Original languageEnglish
Pages (from-to)3970-3979
Number of pages10
JournalJournal of Immunology
Volume156
Issue number10
Publication statusPublished - May 15 1996

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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