Effects of Anaplasma phagocytophila on NADPH oxidase components in human neutrophils and HL-60 cells. 2002

Jason Mott, and Yasuko Rikihisa, and Shohko Tsunawaki
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio 43210-1092, USA.

The human granulocytic ehrlichiosis agent, Anaplasma phagocytophila, resides and multiplies exclusively in cytoplasmic vacuoles of granulocytes. A. phagocytophila rapidly inhibits the superoxide anion (O(2)(-)) generation by human neutrophils in response to various stimuli. To determine the inhibitory mechanism, the influence of A. phagocytophila on protein levels and localization of components of the NADPH oxidase were examined. A. phagocytophila decreased levels of p22(phox), but not gp91(phox), p47(phox), p67(phox), or P40(phox) reactive with each component-specific antibody in human peripheral blood neutrophils and HL-60 cells. Double immunofluorescence labeling revealed that p47(phox), p67(phox), Rac2, and p22(phox) did not colocalize with A. phagocytophila inclusions in neutrophils or HL-60 cells, and p22(phox) levels were also reduced. A. phagocytophila did not prevent either membrane translocation of cytoplasmic p47(phox) and p67(phox) or phosphorylation of p47(phox) upon stimulation by phorbol myristate acetate. The inhibitory signals for O(2)(-) generation was independent of several signals required for A. phagocytophila internalization. These results suggest that rapid alteration in p22(phox) induced by binding of A. phagocytophila to neutrophils is involved in the inhibition of O(2)(-) generation. Absence of colocalization of NADPH oxidase components with the inclusion further protects A. phagocytophila from oxidative damage.

UI MeSH Term Description Entries
D009252 NADPH Dehydrogenase A flavoprotein that reversibly oxidizes NADPH to NADP and a reduced acceptor. EC 1.6.99.1. NADP Dehydrogenase,NADP Diaphorase,NADPH Diaphorase,Old Yellow Enzyme,TPN Diaphorase,Dehydrogenase, NADP,Dehydrogenase, NADPH,Diaphorase, NADP,Diaphorase, NADPH,Diaphorase, TPN,Enzyme, Old Yellow
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D010587 Phagocytosis The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES). Phagocytoses
D010750 Phosphoproteins Phosphoprotein
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000709 Anaplasma A genus of gram-negative bacteria whose organisms are obligate parasites of vertebrates. Species are transmitted by arthropod vectors with the host range limited to ruminants. Anaplasma marginale is the most pathogenic species and is the causative agent of severe bovine anaplasmosis.
D013755 Tetradecanoylphorbol Acetate A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA. Phorbol Myristate Acetate,12-Myristoyl-13-acetylphorbol,12-O-Tetradecanoyl Phorbol 13-Acetate,Tetradecanoylphorbol Acetate, 4a alpha-Isomer,12 Myristoyl 13 acetylphorbol,12 O Tetradecanoyl Phorbol 13 Acetate,13-Acetate, 12-O-Tetradecanoyl Phorbol,Acetate, Phorbol Myristate,Acetate, Tetradecanoylphorbol,Myristate Acetate, Phorbol,Phorbol 13-Acetate, 12-O-Tetradecanoyl,Tetradecanoylphorbol Acetate, 4a alpha Isomer
D016873 Ehrlichiosis A tick-borne disease characterized by FEVER; HEADACHE; myalgias; ANOREXIA; and occasionally RASH. It is caused by several bacterial species and can produce disease in DOGS; CATTLE; SHEEP; GOATS; HORSES; and humans. The primary species causing human disease are EHRLICHIA CHAFFEENSIS; ANAPLASMA PHAGOCYTOPHILUM; and Ehrlichia ewingii. E chaffeensis Infection,E ewingii Infection,E. chaffeensis Infection,E. ewingii Infection,Ehrlichia Infection,Ehrlichia chaffeensis Infection,Ehrlichia ewingii Infection,Human Ehrlichiosis,E chaffeensis Infections,E ewingii Infections,E. ewingii Infections,Ehrlichia Infections,Ehrlichia chaffeensis Infections,Ehrlichia ewingii Infections,Ehrlichioses,Human Ehrlichioses,Infection, E chaffeensis,Infection, E. chaffeensis,Infections, E chaffeensis
D016897 Respiratory Burst A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent (GRANULOMATOUS DISEASE, CHRONIC) often die as a result of recurrent bacterial infections. Oxidative Burst,Burst, Oxidative,Burst, Respiratory,Bursts, Oxidative,Bursts, Respiratory,Oxidative Bursts,Respiratory Bursts

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