Pivotal role of mast cells in pruritogenesis in patients with myeloproliferative disorders

Takefumi Ishii, Jiapeng Wang, Wei Zhang, John Mascarenhas, Ronald Hoffman, Ying Dai, Nathaniel Wisch, Mingjiang Xu

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Pruritus is a common symptom in patients with Philadelphia chromosome-negative myeloproliferative disorders (MPDs). The pathophysiology of MPD-associated pruritus is unclear. We have demonstrated that MPD mast cells (MCs) are involved by the malignant process. In the present study, we explored the hypothesis that MCs play an important role in the development of pruritogenesis in MPDs. We found that MPD MCs released significantly greater amounts of pruritogenic factors, including histamine, leukotrienes, and interleukin-31 (IL-31) than normal MCs. Elevated levels of IL-31 were also observed in MPD CD3+ cell-conditioned media. MPD MCs exhibited increased migratory behavior in response to stem cell factor or interleukin-8, which was associated with increased filamentous-actin content. Furthermore, the presence of pruritus in MPDs was statistically correlated with a greater number of MCs being generated by CD34+ cells, a greater number of MC colonies being formed by CD34+ cells, decreased apoptosis and prostaglandin D2 release by cultured MCs, and higher plasma levels of IL-31. These data demonstrate that functional abnormalities of MPD MCs probably lead to pruritogenesis in patients with MPDs. These studies provide cellular and molecular targets for the development of antipruritus drugs for patients with MPDs.

Original languageEnglish (US)
Pages (from-to)5942-5950
Number of pages9
JournalBlood
Volume113
Issue number23
DOIs
StatePublished - Nov 17 2009

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Ishii, T., Wang, J., Zhang, W., Mascarenhas, J., Hoffman, R., Dai, Y., Wisch, N., & Xu, M. (2009). Pivotal role of mast cells in pruritogenesis in patients with myeloproliferative disorders. Blood, 113(23), 5942-5950. https://doi.org/10.1182/blood-2008-09-179416