The cation channel TRPM8 influences the differentiation and function of human monocytes

被引:8
作者
Hornsby, Eve [1 ,2 ]
King, Hamish W. [1 ,2 ]
Peiris, Madusha [3 ]
Buccafusca, Roberto [4 ]
Lee, Wing-Yiu Jason [1 ,2 ]
Wing, Elinor S. [1 ,2 ]
Blackshaw, L. Ashley [3 ]
Lindsay, James O. [1 ,2 ,5 ]
Stagg, Andrew J. [1 ,2 ]
机构
[1] Queen Mary Univ London, Ctr Immunobiol, London E1 2AT, England
[2] Queen Mary Univ London, Barts & London Sch Med & Dent, London E1 2AT, England
[3] Queen Mary Univ London, Ctr Neurosci & Trauma, Blizard Inst, Barts & London Sch Med & Dent, London, England
[4] Queen Mary Univ London, Sch Biol & Chem Sci, Mile End Rd, London, England
[5] Barts Hlth NHS Trust, Royal London Hosp, Dept Gastroenterol, London, England
关键词
LPS; monocyte-derived macrophage; phagocytosis; TRP channels; DENDRITIC CELLS; STEADY-STATE; CARDIAC MACROPHAGES; PROSTATE-CANCER; ION-CHANNEL; ACTIVATION; IDENTIFICATION; PROLIFERATION; PROTECTION; INFECTION;
D O I
10.1002/JLB.1HI0421-181R
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Monocytes are mononuclear phagocytes that can differentiate to a variety of cell fates under the influence of their microenvironment and hardwired commitment. We found that inhibition of TRPM8 in human blood CD14(+) monocytes during a critical 3-h window at the beginning of their differentiation into macrophages led to enhanced survival and LPS-driven TNF alpha production after 24 h. TRPM8 antagonism also promoted LPS-driven TNF alpha production in CD14(+) monocytes derived from the intestinal mucosa. Macrophages that had been derived for 6 days under blockade of TRPM8 had impaired phagocytic capacity and were transcriptionally distinct. Most of the affected genes were altered in a way that opposed normal monocyte to macrophage differentiation indicating that TRPM8 activity promotes aspects of this differentiation programme. Thus, we reveal a novel role for TRPM8 in regulating human CD14(+) monocyte fate and function.
引用
收藏
页码:365 / 381
页数:17
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