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.

[1]  A. Komiyama,et al.  CD27: a memory B-cell marker. , 2000, Immunology today.

[2]  G. Murphy,et al.  Metalloproteinase-mediated Regulation of L-selectin Levels on Leucocytes (*) , 1996, The Journal of Biological Chemistry.

[3]  F. Chiodi,et al.  Plasma levels of soluble CD27: a simple marker to monitor immune activation during potent antiretroviral therapy in HIV‐1‐infected subjects , 2002, Clinical and experimental immunology.

[4]  I. T. Ten Berge,et al.  A soluble form of the human T cell differentiation antigen CD27 is released after triggering of the TCR/CD3 complex. , 1991, Journal of immunology.

[5]  G. Dubyak,et al.  Stress-activated protein kinase/JNK activation and apoptotic induction by the macrophage P2X7 nucleotide receptor. , 2000, The Journal of biological chemistry.

[6]  J. Wiley,et al.  Adenosine triphosphate-induced shedding of CD23 and L-selectin (CD62L) from lymphocytes is mediated by the same receptor but different metalloproteases. , 1998, Blood.

[7]  C. Morimoto,et al.  B cell subpopulations separated by CD27 and crucial collaboration of CD27+ B cells and helper T cells in immunoglobulin production , 1997, European journal of immunology.

[8]  E. Leiter,et al.  P2X7 Receptor-Dependent and -Independent T Cell Death Is Induced by Nicotinamide Adenine Dinucleotide1 , 2005, The Journal of Immunology.

[9]  N. Kendrick,et al.  ATP-induced killing of mycobacteria by human macrophages is mediated by purinergic P2Z(P2X7) receptors. , 1997, Immunity.

[10]  R. V. van Lier,et al.  Constitutive CD27/CD70 interaction induces expansion of effector-type T cells and results in IFNgamma-mediated B cell depletion. , 2001, Immunity.

[11]  R. V. van Lier,et al.  The CD27 membrane receptor, a lymphocyte‐specific member of the nerve growth factor receptor family, gives rise to a soluble form by protein processing that does not involve receptor endocytosis , 1992, European journal of immunology.

[12]  J. Borst,et al.  CD27 Is Acquired by Primed B Cells at the Centroblast Stage and Promotes Germinal Center Formation1 , 2004, The Journal of Immunology.

[13]  J. Martorell.,et al.  Elevated soluble CD27 levels in serum of patients with systemic lupus erythematosus. , 1996, Clinical immunology and immunopathology.

[14]  J. Wiley,et al.  Extracellular adenosine 5'-triphosphate induces a loss of CD23 from human dendritic cells via activation of P2X7 receptors. , 2002, International immunology.

[15]  J. Borst,et al.  CD27 Promotes Survival of Activated T Cells and Complements CD28 in Generation and Establishment of the Effector T Cell Pool , 2003, The Journal of experimental medicine.

[16]  T. Schumacher,et al.  CD27 is required for generation and long-term maintenance of T cell immunity , 2000, Nature Immunology.

[17]  F. Di Virgilio,et al.  Mouse dendritic cells express the P2X7 purinergic receptor: characterization and possible participation in antigen presentation. , 1999, Journal of immunology.

[18]  P. Dempsey,et al.  A Disintegrin and Metalloproteinase 10-Mediated Cleavage and Shedding Regulates the Cell Surface Expression of CXC Chemokine Ligand 16 , 2004, The Journal of Immunology.

[19]  K. Jung,et al.  Characterization and epitope mapping of two monoclonal antibodies against human CD99 , 2002, Experimental & Molecular Medicine.

[20]  G. Burnstock,et al.  Increased release of ATP from endothelial cells during acute inflammation , 1998, Inflammation Research.

[21]  R. V. van Lier,et al.  Tissue distribution and biochemical and functional properties of Tp55 (CD27), a novel T cell differentiation antigen. , 1987, Journal of immunology.

[22]  K. Agematsu,et al.  Synergistic augmentative effect of interleukin‐10 and CD27/CD70 interactions on B‐cell immunoglobulin synthesis , 1998, Immunology.

[23]  P. Parnet,et al.  Maturation and Release of Interleukin-1β by Lipopolysaccharide-primed Mouse Schwann Cells Require the Stimulation of P2X7 Receptors* , 2003, Journal of Biological Chemistry.

[24]  R. North.  Molecular physiology of P2X receptors. , 2002, Physiological reviews.

[25]  F. Di Virgilio,et al.  Nucleotide receptors: an emerging family of regulatory molecules in blood cells. , 2001, Blood.

[26]  C. Morimoto,et al.  CD27-CD70 interactions regulate B-cell activation by T cells. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[27]  N. Chiorazzi,et al.  S152 (CD27). A modulating disulfide-linked T cell activation antigen. , 1988, Journal of immunology.

[28]  R. North,et al.  Rapid secretion of interleukin-1β by microvesicle shedding , 2001 .

[29]  M. Seman,et al.  Cutting Edge: A Natural P451L Mutation in the Cytoplasmic Domain Impairs the Function of the Mouse P2X7 Receptor1 , 2002, The Journal of Immunology.

[30]  K. Rajewsky,et al.  Human Immunoglobulin (Ig)M+IgD+ Peripheral Blood B Cells Expressing the CD27 Cell Surface Antigen Carry Somatically Mutated Variable Region Genes: CD27 as a General Marker for Somatically Mutated (Memory) B Cells , 1998, The Journal of experimental medicine.

[31]  R. Paus,et al.  Signaling through P2X7 Receptor in Human T Cells Involves p56 lck , MAP Kinases, and Transcription Factors AP-1 and NF-κB* , 2003, Journal of Biological Chemistry.

[32]  F. Di Virgilio,et al.  Increased Proliferation Rate of Lymphoid Cells Transfected with the P2X7 ATP Receptor* , 1999, The Journal of Biological Chemistry.

[33]  M. Seman,et al.  NAD-induced T cell death: ADP-ribosylation of cell surface proteins by ART2 activates the cytolytic P2X7 purinoceptor. , 2003, Immunity.

[34]  G. Weskamp,et al.  Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR ligands , 2004, The Journal of cell biology.

[35]  A. Martini,et al.  Levels of soluble CD27 in sera and synovial fluid and its expression on memory T cells in patients with juvenile idiopathic arthritides. , 2002, Clinical and experimental rheumatology.

[36]  C. Higgins,et al.  Major histocompatibility complex class I shedding and programmed cell death stimulated through the proinflammatory P2X7 receptor: a candidate susceptibility gene for NOD diabetes. , 2004, Diabetes.

[37]  T. van der Poll,et al.  The Metalloproteinase Inhibitor GI5402 Inhibits Endotoxin-Induced Soluble CD27 and CD16 Release in Healthy Humans , 2000, Infection and Immunity.

[38]  J. Borst,et al.  Lethal T cell immunodeficiency induced by chronic costimulation via CD27-CD70 interactions , 2003, Nature Immunology.

[39]  G. Kollias,et al.  Tumor Necrosis Factor (TNF) Receptor Shedding Controls Thresholds of Innate Immune Activation That Balance Opposing TNF Functions in Infectious and Inflammatory Diseases , 2004, The Journal of experimental medicine.