Resistance of CD4-positive T lymphocytes to etoposide-induced apoptosis mediated by upregulation of Bcl-xL expression in patients with HTLV-I-associated myelopathy.
Human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) is characterized by chronic inflammation of the spinal cord. The exact mechanisms that enhance the development of chronic myelopathy remain to be determined. One such mechanism could be an altered response of peripheral blood CD4(+) T lymphocytes to apoptotic stimuli. We examined the sensitivity of these cells to apoptosis in HAM patients and control. Apoptosis was induced by etoposide, which induces mitochondria-dependent apoptosis through the release of cytochrome c from the mitochondria. The percentage of apoptotic cells that expressed hypodiploid DNA among etoposide-treated CD4(+) T lymphocytes was significantly lower in HAM patients than in the control. Western blot analysis of cell lysates derived from CD4(+) T lymphocytes demonstrated that the expression level of Bcl-xL protein was significantly higher in HAM patients than in the control. Our results indicate that peripheral blood CD4(+) T lymphocytes of HAM patients are resistant to apoptosis triggered through mitochondrial death pathway through upregulation of expression of anti-apoptotic protein, Bcl-xL. This phenomenon might contribute to the prolongation and perpetuation of the chronic inflammatory process in the spinal cord of HAM patients.
Hamasaki
S
S
First Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, 852-8501, Nagasaki, Japan.
Nakamura
T
T
Furuya
T
T
Kawakami
A
A
Ichinose
K
K
Nakashima
T
T
Nishiura
Y
Y
Shirabe
S
S
Eguchi
K
K
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D005047:Etoposide / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D015854:Up-Regulation; D051020:bcl-X Protein; D019014:fas Receptor / Q000502:physiology
D000972:Antineoplastic Agents, Phytogenic; C494811:BCL2L1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D019014:fas Receptor; D005047:Etoposide