P2X7 receptor-dependent ATP-induced shedding of CD27 in mouse lymphocytes.
The ATP-gated P2X7 cell surface receptor belongs to the P2X purinoreceptor family, and is expressed abundantly by immune cells. This receptor is involved in several inflammatory and immunological processes, including the secretion of IL-1 by activated macrophages. Here, we demonstrate that CD27, a cell surface molecule, which is involved in the interaction between immune cells and implicated in the immunological memory of the T and B cells, is released rapidly upon treatment with low ATP concentrations, via the activation of the P2X7 receptor. The surface expression of CD27 on the T and B cells has been shown to be down-regulated as the result of ATP treatment, and the soluble form of CD27 was detected readily in the supernatants of splenocytes, which were cultured along with ATP treatment. The shedding of CD27 was blocked by KN-62, a chemical P2X7 inhibitor, and was also efficiently triggered by treatment with 2,3-O-(4-benzoyl-benzoyl)-ATP. The shedding of CD27 from mouse splenic T cells was observed to occur within 5 min of treatment with 300 microM ATP, whereas treatment with PMA or ionomycin was not determined to trigger the shedding of CD27 until treatment had been applied for a period of at least 2 h. The ATP-induced shedding of CD27 was inhibited by treatment with the matrix metalloprotease inhibitor, GM6001, but not by treatments with BAPTA-AM, wortmannin, SB202190, or PD 98059. Therefore, we concluded that P2X7 receptor stimulation by extracellular ATP results in rapid CD27 shedding via protease activation.
Moon
Hana
H
Laboratory of Immunopathology, Department of Molecular Cell Biology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea.
Na
Hye-Young
HY
Chong
Kyung Hee
KH
Kim
Tae Jin
TJ
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D051379:Mice; D010447:Peptide Hydrolases / Q000378:metabolism; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
C546469:P2rx7 protein, mouse; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D000255:Adenosine Triphosphate; D010447:Peptide Hydrolases