title: NTPDase1 activity attenuates microglial phagocytosis.
abstract: Purinergic signaling plays a major role in the regulation of phagocytosis in microglia. Interplay between P2 and P1 receptor activation is controlled by a cascade of extracellular enzymes which dephosphorylate purines resulting in the formation of adenosine. The ATP- and ADP-degrading capacity of cultured microglia depends on the expression of ecto-nucleoside triphosphate diphosphohydrolase 1 (CD39) and is several times higher when compared to astrocytes which lack this enzyme. In brain slices, deletion of CD39 resulted in a 50 % decrease of ADP-degrading ability, while the degradation of ATP was decreased to about 75 % of the values measured in wild-type brain tissue. Microglia in acute slices from cd39(-/-) animals had increased constitutive phagocytic activity which could not be further enhanced by ATP in contrast to control animals. Pharmacological blockage of P2 receptors decreased the constitutive phagocytic activity to a similar base level in wild-type and cd39(-/-) microglia. Activation of P1 receptors by non-hydrolysable adenosine analog significantly decreased phagocytic activity. Deletion of CD73, an enzyme expressed by microglia which converts AMP to adenosine did not affect phagocytic activity. Taken together, these data show that CD39 plays a prominent role in controlling ATP levels and thereby microglial phagocytosis.
authors.affiliation: Department for Cellular Neurosciences, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
authors.forename: Larisa
authors.initials: L
authors.lastname: Bulavina
authors.forename: Frank
authors.initials: F
authors.lastname: Szulzewsky
authors.forename: Adriana
authors.initials: A
authors.lastname: Rocha
authors.forename: Grietje
authors.initials: G
authors.lastname: Krabbe
authors.forename: Simon C
authors.initials: SC
authors.lastname: Robson
authors.forename: Vitali
authors.initials: V
authors.lastname: Matyash
authors.forename: Helmut
authors.initials: H
authors.lastname: Kettenmann
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001081:Apyrase / Q000378:metabolism*; D002478:Cells, Cultured; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism*; D018613:Microscopy, Confocal; D009924:Organ Culture Techniques; D010587:Phagocytosis / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D000255:Adenosine Triphosphate; D001081:Apyrase; C067869:CD39 antigen