期刊
BRITISH JOURNAL OF HAEMATOLOGY
卷 163, 期 1, 页码 81-92出版社
WILEY
DOI: 10.1111/bjh.12475
关键词
monocytes; bone marrow; cytokines; immunology; inherited bone marrow failure syndromes
类别
资金
- Fanconi Anaemia Research Fund
- National Institutes of Health
- National Cancer Institute
- Westat, Incorporated [N02-CP-91026, N02-CP-11019, HHSN261200655001C]
- National Cancer Institute, National Institutes of Health [HHSN261200800001E]
Fanconi anaemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anaemia (DBA), and Shwachman-Diamond syndrome (SDS) are characterized by the progressive development of bone marrow failure. Overproduction of tumour necrosis factor-alpha (TNF-alpha) from activated bone marrow T-cells has been proposed as a mechanism of FA-related aplasia. Whether such overproduction occurs in the other syndromes is unknown. We conducted a comparative study on bone marrow mononuclear cells to examine the cellular subset composition and cytokine production. We found lower proportions of haematopoietic stem cells in FA, DC, and SDS, and a lower proportion of monocytes in FA, DC, and DBA compared with controls. The T- and B-lymphocyte proportions were similar to controls, except for low B-cells in DC. We did not observe overproduction of TNF-alpha or IFN-gamma by T-cells in any patients. Induction levels of TNF-alpha, interleukin (IL)-6, IL-1 beta, IL-10, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor in monocytes stimulated with high-dose lipopolysaccharide (LPS) were similar at 4h but lower at 24h when compared to controls. Unexpectedly, patient samples showed a trend toward higher cytokine level in response to low-dose (0 center dot 001 mu g/ml) LPS. Increased sensitivity to LPS may have clinical implications and could contribute to the development of pancytopenia by creating a chronic subclinical inflammatory micro-environment in the bone marrow.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据