Pivotal role of mast cells in pruritogenesis in patients with myeloproliferative disorders.
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 D(2) 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.
Ishii
Takefumi
T
Division of Hematology/Oncology, Tisch Cancer Institute and Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
Wang
Jiapeng
J
Zhang
Wei
W
Mascarenhas
John
J
Hoffman
Ronald
R
Dai
Ying
Y
Wisch
Nathaniel
N
Xu
Mingjiang
M
D000199:Actins / Q000378:metabolism; D000483:Alleles; D002465:Cell Movement; D006632:Histamine / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000097:blood; D007378:Interleukins / Q000096:biosynthesis / Q000097:blood; D053614:Janus Kinase 2 / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism*; D009196:Myeloproliferative Disorders / Q000378:metabolism* / Q000473:pathology; D020932:Nerve Growth Factor / Q000097:blood; D015230:Prostaglandin D2 / Q000378:metabolism; D053802:Tryptases / Q000378:metabolism
D000199:Actins; C502187:IL31 protein, human; D007378:Interleukins; D015289:Leukotrienes; D015847:Interleukin-4; D006632:Histamine; D020932:Nerve Growth Factor; D053614:Janus Kinase 2; D053802:Tryptases; D015230:Prostaglandin D2