组胺缺乏在肿瘤的影响.ppt

Histamine Deficiency Promotes Inflammation-associated Carcinogenesis He Yi 2011/4/21 Introduction ☆ Histamine is a biogenic amine that has well defined roles in allergic responses and has also been linked to the modulation of immune responses such as regulating T cells. Endogenous histamine is generated through conversion of L-histidine to histamine by the action of a unique enzyme, HDC. And it is believed to have an immune regulatory function in myeloid cells. Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b+Ly6G+ immature myeloid cells. ☆ Histamine deficiency Reduced myeloid maturation Accumulation of CD11b+Ly6G+ IMCs Carcinogenesis Little is known regarding the role of histamine in carcinogenesis. Although Excessive histamine release are reported to have a reduced incidence of cancer, the mechanisms remain unclear. Here we report that Hdc is primarily expressed in CD11b+Ly6G+ IMCs within the bone marrow where histamine promotes myeloid cell differentiation leading to suppression of ☆ ☆ Myeloid cells are a major component of tumor masses and are pivotal in promoting tumor progression. In the bone marrow, CD11b+Gr-1+ IMCs are thought to represent myeloid precursor cells. The myeloid lineage includes both monocytic cells and granulocytic cells. And Tumorigenesis in mice is associated with the recruitment of CD11b+Ly6G+ tumor-associated neutrophils. cancer formation. CD11b+Gr-1+ IMCs CD11b+Ly6G+ Granulocytic cells CD11b+Ly6C+ Monocytic cells ☆ Results ☆ Histamine-deficient Hdc?/? mice are highly susceptible to colore-ctal carcinogenesis. (a) Macroscopic appearance of colorectal tumors from wild-type (WT) and Hdc?/? mice. Hdc?/? mice and wild-type mice were injected with a single dose of AOM followed by DSS in the drinking water for 10 d. (b) The number of large (diameter 3 mm) and small (diameter 3 mm) colorectal tumors in Hdc?/? mice versus wild-type mice (*P