Accession Number:

ADA604192

Title:

The Role of Necroptosis in the Pathophysiology of Bone Marrow Failure

Descriptive Note:

Annual rept. 6 Feb 2013-5 Feb 2014

Corporate Author:

LOYOLA UNIV MAYWOOD IL

Personal Author(s):

• Zhang, Jiwang

Report Date:

2014-03-01

Pagination or Media Count:

8.0

Abstract:

We proposed that 1 persistent spontaneous necroptosis in a very small number of hematopoietic cells might be the cause of BMF syndromes 2 necroptotic cells release molecules which trigger the onset of T cell-dependent adaptive immune reactions causing BMF syndromes 3 immune cells suppress BM hematopoiesis by producing inflammatory cytokines, including IFN-gamma and TNF-alpha The dynamic alteration of IFN-gamma and TNF-alpha levels might determine disease progression in BMF syndromes. To address such hypotheses, We propose to use the chronic BMF model of our CTakfx to study 1 the role of necroptosis in the pathogenesis of BMF in CTakfx mice by examining whether the inhibition of necroptosis can prevent BMF in such mice 2 how IFN-gamma and TNF-alpha-induced signals are communicated in hematopoietic regulation and contribute to the BMF phenotype in CTakfx mice 3 whether immune-mediated hematopoietic destruction contributes to the pathogenesis of BMF in CTakfx mice. Current conclusion CD4 activated T cells, CD4 memory T cells, and CD4 Th1 T cells are significantly increased in CTakfx mice. Such cells might be the cause of BMF in CTakfx mice, because depletion of CD4 T cells by anti-CD4 antibody treatment can almost complete restore normal hematopoiesis in CTakfx mice.

Descriptors:

• *BONE MARROW
• ANTIBODIES
• CYTOKINES
• FAILURE
• HEMATOPOIESIS
• INFLAMMATION
• PATHOGENESIS
• PATHOPHYSIOLOGY
• T LYMPHOCYTES

Subject Categories:

• Anatomy and Physiology
• Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE