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Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b +Ly6G+ immature myeloid cells
Nature Medicine
  • Xiang Dong Yang, Columbia University
  • Walden Ai, Columbia University
  • Samuel Asfaha, Columbia University
  • Govind Bhagat, Columbia University
  • Richard A. Friedman, Columbia University
  • Guangchun Jin, Columbia University
  • Heuijoon Park, Columbia University
  • Benjamin Shykind, Columbia University
  • Thomas G. Diacovo, Columbia University
  • Andras Falus, Semmelweis Egyetem
  • Timothy C. Wang, Columbia University
Document Type
Article
Publication Date
1-1-2011
URL with Digital Object Identifier
10.1038/nm.2278
Disciplines
Abstract

Histidine decarboxylase (HDC), the unique enzyme responsible for histamine generation, is highly expressed in myeloid cells, but its function in these cells is poorly understood. Here we show that Hdc-knockout mice show a high rate of colon and skin carcinogenesis. Using Hdc-EGFP bacterial artificial chromosome (BAC) transgenic mice in which EGFP expression is controlled by the Hdc promoter, we show that Hdc is expressed primarily in CD11b +Ly6G+ immature myeloid cells (IMCs) that are recruited early on in chemical carcinogenesis. Transplant of Hdc-deficient bone marrow to wild-type recipients results in increased CD11b + Ly6G + cell mobilization and reproduces the cancer susceptibility phenotype of Hdc-knockout mice. In addition, Hdc-deficient IMCs promote the growth of tumor allografts, whereas mouse CT26 colon cancer cells downregulate Hdc expression through promoter hypermethylation and inhibit myeloid cell maturation. Exogenous histamine induces the differentiation of IMCs and suppresses their ability to support the growth of tumor allografts. These data indicate key roles for Hdc and histamine in myeloid cell differentiation and CD11b+Ly6G+IMCs in early cancer development. © 2011 Nature America, Inc. All rights reserved.

Citation Information
Xiang Dong Yang, Walden Ai, Samuel Asfaha, Govind Bhagat, et al.. "Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b +Ly6G+ immature myeloid cells" Nature Medicine Vol. 17 Iss. 1 (2011) p. 87 - 95
Available at: http://works.bepress.com/samuel-asfaha/15/