Natural killer cell degranulation and lytic proteins in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
Author(s)
Huth, Teilah Kathryn
Brenu, Ekua
Fuller, Kirsty
Hardcastle, Sharni Lee
Johnston, Samantha
Staines, Don
Marshall-Gradisnik, Sonya
Griffith University Author(s)
Year published
2014
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Objectives: Reduced Natural Killer (NK) cell cytotoxic activity is a recurring finding in patients with Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS/ME). NK cell cytotoxic activity is important for removing virally infected or malignantly transformed cells and a critical component of NK cell cytotoxic activity is the release of the lytic proteins perforin, granzyme A and granzyme B by a process known as degranulation. This study measured NK cell perforin, granzyme A, granzyme B and degranulation in CFS/ME patients to determine whether lytic proteins or degranulation may contribute to the reduced NK cell cytotoxic ...
View more >Objectives: Reduced Natural Killer (NK) cell cytotoxic activity is a recurring finding in patients with Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS/ME). NK cell cytotoxic activity is important for removing virally infected or malignantly transformed cells and a critical component of NK cell cytotoxic activity is the release of the lytic proteins perforin, granzyme A and granzyme B by a process known as degranulation. This study measured NK cell perforin, granzyme A, granzyme B and degranulation in CFS/ME patients to determine whether lytic proteins or degranulation may contribute to the reduced NK cell cytotoxic activity in CFS/ME patients. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 30 CFS (mean age = 51.15±1.92 years) and 25 non-fatigued controls (mean age = 50.42±1.76 years). NK cell perforin, granzyme A and granzyme B levels were determined by intracellular staining and NK cells were stimulated to degranulate with K562 cells and phorbol 12-myristate 13-acetate/ionomycin (PMA/I) for 6 hours. NK cell degranulation was measured by surface expression of CD107a and NK (CD56+CD3-) cell levels of perforin, granzyme A, granzyme B and CD107a was determined with flow cytometric protocols. Results: A significant increase (P<0.05) in NK cell expression of CD107a was observed in CFS/ME patients following stimulation with PMA/I and K562 cells. No significant differences in NK cell perforin and granzyme A were observed between the non-fatigued controls and CFS/ME patients. However, granzyme B in NK cells from CFS/ME patients was significantly reduced (P<0.05). Conclusion: These results indicate that the aberrant function of NK cell lytic proteins and degranulation may contribute to the reduced NK cell cytotoxic activity reported in CFS/ME patients. Further investigations are required to determine if there is a correlation between dysfunctional NK cell degranulation and release of the lytic proteins required to induce target cell apoptosis.
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View more >Objectives: Reduced Natural Killer (NK) cell cytotoxic activity is a recurring finding in patients with Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS/ME). NK cell cytotoxic activity is important for removing virally infected or malignantly transformed cells and a critical component of NK cell cytotoxic activity is the release of the lytic proteins perforin, granzyme A and granzyme B by a process known as degranulation. This study measured NK cell perforin, granzyme A, granzyme B and degranulation in CFS/ME patients to determine whether lytic proteins or degranulation may contribute to the reduced NK cell cytotoxic activity in CFS/ME patients. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 30 CFS (mean age = 51.15±1.92 years) and 25 non-fatigued controls (mean age = 50.42±1.76 years). NK cell perforin, granzyme A and granzyme B levels were determined by intracellular staining and NK cells were stimulated to degranulate with K562 cells and phorbol 12-myristate 13-acetate/ionomycin (PMA/I) for 6 hours. NK cell degranulation was measured by surface expression of CD107a and NK (CD56+CD3-) cell levels of perforin, granzyme A, granzyme B and CD107a was determined with flow cytometric protocols. Results: A significant increase (P<0.05) in NK cell expression of CD107a was observed in CFS/ME patients following stimulation with PMA/I and K562 cells. No significant differences in NK cell perforin and granzyme A were observed between the non-fatigued controls and CFS/ME patients. However, granzyme B in NK cells from CFS/ME patients was significantly reduced (P<0.05). Conclusion: These results indicate that the aberrant function of NK cell lytic proteins and degranulation may contribute to the reduced NK cell cytotoxic activity reported in CFS/ME patients. Further investigations are required to determine if there is a correlation between dysfunctional NK cell degranulation and release of the lytic proteins required to induce target cell apoptosis.
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Conference Title
Natural killer cell degranulation and lytic proteins in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
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Subject
Cellular Immunology