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CHARACTERIZATION OF THE ROLE OF HAX1 IN NEUTROPHIL APOPTOSIS

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Date Issued:
2017
Summary:
Severe congenital neutropenia is a heterogeneous syndrome which causes a life-threatening scarcity of neutrophils. Kostmann Syndrome is an inheritable, autosomal recessive form of neutropenia, characterized by myelocyte maturation arrest caused by mutations to the anti-apoptotic gene HAX1 (Klein et al. 2007). Even with treatment, other disorders such as bone disease, leukemia, and marrow cancer occur. Loss of function mutations to the HAX1 gene negate the anti-apoptotic characteristics of Hax1, like protection of the mitochondrial membrane potential and interactions with proteins involved in controlled death or survival. Apoptosis plays an important role in SCN pathogenesis, cancer, and normal immune regulation, so researchers have sought to understand the mechanisms behind neutrophil regulation of immune response, response to pro-survival chemoattractants, and Hax1 function. In this thesis, I studied the effect of immune mediators, LPS, C5a, and fMLP in the myeloid leukemia cell line PLB-985, differentiated into a neutrophil-like cell with DMSO. Using shRNAs to knock down Hax1 expression, our results support the previous research that Hax1 contributes to delay of apoptosis. Contrary to literature describing the pro-survival effect of exposure to LPS and C5a in primary neutrophils, we found no significant difference in the level of apoptosis of cells exposed to LPS, C5a, or fMLP
Title: CHARACTERIZATION OF THE ROLE OF HAX1 IN NEUTROPHIL APOPTOSIS.
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Name(s): Inman, Kristina Anne, Author
Type of Resource: text
Date Issued: 2017
Publisher: University of West Florida
Language(s): English
Summary: Severe congenital neutropenia is a heterogeneous syndrome which causes a life-threatening scarcity of neutrophils. Kostmann Syndrome is an inheritable, autosomal recessive form of neutropenia, characterized by myelocyte maturation arrest caused by mutations to the anti-apoptotic gene HAX1 (Klein et al. 2007). Even with treatment, other disorders such as bone disease, leukemia, and marrow cancer occur. Loss of function mutations to the HAX1 gene negate the anti-apoptotic characteristics of Hax1, like protection of the mitochondrial membrane potential and interactions with proteins involved in controlled death or survival. Apoptosis plays an important role in SCN pathogenesis, cancer, and normal immune regulation, so researchers have sought to understand the mechanisms behind neutrophil regulation of immune response, response to pro-survival chemoattractants, and Hax1 function. In this thesis, I studied the effect of immune mediators, LPS, C5a, and fMLP in the myeloid leukemia cell line PLB-985, differentiated into a neutrophil-like cell with DMSO. Using shRNAs to knock down Hax1 expression, our results support the previous research that Hax1 contributes to delay of apoptosis. Contrary to literature describing the pro-survival effect of exposure to LPS and C5a in primary neutrophils, we found no significant difference in the level of apoptosis of cells exposed to LPS, C5a, or fMLP
Identifier: WFE0000574 (IID), uwf:61179 (fedora)
Note(s): 2017-07-01
M.S.
Department of Biology
Masters
Persistent Link to This Record: http://purl.flvc.org/uwf/fd/WFE0000574
Restrictions on Access: public
Use and Reproduction: http://rightsstatements.org/vocab/InC-EDU/1.0/
Host Institution: UWF

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