The P2X7 purinergic receptor on bovine macrophages mediates mycobacterial death.
P2X7 is an ATP gated purinoceptor that has been linked to various immune responses. P2X7 appears to be expressed ubiquitously in the immune system and thus may be important as an effector pathway or play significant roles in cell activation/death. 2',3'-(4-Benzoyl)benzoyl ATP is the most potent agonist of this receptor and ATP in its fully dissociated form (ATP(4-)) also activates the receptor. High concentrations of ATP can cause the P2X7 receptor to induce pore formation on the surface of the cell that allows molecules of considerable size to pass and can lead to cell death. The P2X7 receptor has also been linked to various immune activities when the concentration of ATP is lower, including the release of IL-1beta. The role P2X7 receptors have on immune cell activities is just beginning to be understood. We sought to determine the role of P2X7 on bovine macrophages in eliminating the causative agent of bovine-type tuberculosis, Mycobacterium bovis. Because high concentrations of ATP are linked to macrophage death, we determined if this method of cell destruction also leads to reduced bacterial viability. We find that P2X7 is present on bovine macrophages from different sources, including both peripheral blood-derived as well as alveolar macrophages. In addition, P2X7 mRNA is present in B and T lymphocytes. The treatment of M. bovis-infected macrophages with ATP results in reduced macrophage viability as well as reduced M. bovis viability.
Smith
R A
RA
Department of Veterinary Pathobiology, Program for Prevention of Animal Infectious Diseases, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA.
Alvarez
A J
AJ
Estes
D M
DM
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D016923:Cell Death; D008264:Macrophages / Q000502:physiology*; D008969:Molecular Sequence Data; D009163:Mycobacterium bovis; D012333:RNA, Messenger / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000502:physiology*; D058486:Receptors, Purinergic P2X7; D014380:Tuberculosis, Bovine / Q000276:immunology
D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate