Extracellular ATP regulates cell death of lymphocytes and monocytes induced by membrane-bound lipoproteins of Mycoplasma fermentans and Mycoplasma salivarium.
The cytotoxicities of lipoproteins of Mycoplasma fermentans and Mycoplasma salivarium to a lymphocytic cell line, MOLT-4, and a monocytic cell line, HL-60, was upregulated by ATP added extracellularly in a dose-dependent manner. These lipoproteins induced ATP release and plasma membrane permeability increase in these cell lines. In addition, periodate-oxidized ATP, an antagonist for P2X purinergic receptors, suppressed the cytotoxicity of the lipoproteins, suggesting the possibility that P2X receptors for ATP play crucial roles in the cytotoxicity. Activation of caspase-3 induced by the lipoproteins, which was assessed by the cleavage of the synthetic substrate DEVD-pNA and the endogenous substrate poly(ADP-ribose) polymerase, was also upregulated and downregulated by extracellular ATP and periodate-oxidized ATP, respectively. On the basis of these results, this study suggests that mycoplasmal lipoproteins induce the permeability increase in lymphocytes and monocytes, by which ATP is released, and the ATP regulates the cytotoxicities of the lipoproteins to the cells, possibly by interaction with ATP receptors such as P2X purinergic receptors.
Into
Takeshi
T
Department of' Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, Sapporo, Hokkaido 060-8586, Japan.
Okada
Kazutaka
K
Inoue
Nobuo
N
Yasuda
Motoaki
M
Shibata
Ken-ichiro
K
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000378:metabolism / Q000633:toxicity; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D005110:Extracellular Space; D005434:Flow Cytometry; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism / Q000633:toxicity*; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism / Q000633:toxicity; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D009175:Mycoplasma Infections / Q000378:metabolism* / Q000382:microbiology; D016858:Mycoplasma fermentans / Q000378:metabolism*; D010539:Permeability; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001426:Bacterial Proteins; D008074:Lipoproteins; D008565:Membrane Proteins; D018048:Receptors, Purinergic P2; C017199:2',3'-dialdehyde ATP; D000255:Adenosine Triphosphate; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases