Mice deficient in phox (gp91(phox-/-)) or NOS2 (NOS2(-/-)) were infected with the agent of human granulocytic ehrlichiosis (HGE) to evaluate the importance of these pathways in the eradication of HGE bacteria. NOS2(-/-) mice had delayed clearance of the HGE agent in comparison to control or gp91(phox-/-) mice, suggesting that reactive nitrogen intermediates play a role in the early control of HGE.

Complement C5-deficient (C5(-/-)) macrophages derived from B.10 congenic mice were found to be defective in killing intracellular Mycobacterium tuberculosis (MTB). They were bacteriostatic after activation with IFN-gamma alone but bactericidal in the combined presence of IFN-gamma and C5-derived C5a anaphylatoxin that was deficient among these macrophages. Reduced killing correlated with a decr...

Upon activation, the NADPH oxidase from neutrophils produces superoxide anions in response to microbial infection. This enzymatic complex is activated by association of its cytosolic factors p67(phox), p47(phox), and the small G protein Rac with a membrane-associated flavocytochrome b(558). Here we report the crystal structure of the active N-terminal fragment of p67(phox) at 1.8 A resolution, ...

The superoxide-producing phagocyte NADPH oxidase consists of a membrane-bound flavocytochrome b(558), the cytosol factors p47(phox), p67(phox), p40(phox), and the small GTPase Rac2, which translocate to the membrane to assemble the active complex following neutrophil activation. Interleukin-8 (IL-8) does not activate NADPH oxidase, but potentiates the oxidative burst induced by stimuli such as ...

BACKGROUND INFORMATION During phagocytosis, neutrophils internalise pathogens in a phagosome and produce reactive oxygen species (ROS) by the NADPH oxidase to kill the pathogen. The cytosolic NADPH oxidase subunits p40(phox), p47(phox), p67(phox) and Rac2 translocate to the phagosomal membrane to participate in enzyme activation. The kinetics of this recruitment and the underlying signalling pa...

Myogenic and angiotensin contractions of afferent arterioles generate reactive oxygen species. Resistance vessels express neutrophil oxidase-2 and -4. Angiotensin II activates p47(phox)/neutrophil oxidase-2, whereas it downregulates NOX-4. Therefore, we tested the hypothesis that p47(phox) enhances afferent arteriolar angiotensin contractions. Angiotensin II infusion in p47(phox) +/+ but not -/...

Infection is a major cause of morbidity and mortality in patients after thermal injury. This predisposition to infections is related, in part, to abnormal polymorphonuclear leukocyte (PMN) function and a diminished respiratory burst. To evaluate the biochemical basis for the defective respiratory burst after major burns, the status of the oxidase enzyme system and its components was investigate...

p40-phox is a newly isolated cytosolic component of the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase that copurifies with p67-phox. Although its function is not well defined, preliminary evidence indicates that it is a component of the cytosolic complex. We report the characterization of the human p40-phox gene, which is single copy and spans approximately 18 kb with 10 exons. Ba...

A component of a heterodimeric cytochrome b, designated gp91-phox, is required for the microbicidal activity of phagocytic cells and is expressed exclusively in differentiated myelomonocytic cells (granulocytes; monocyte/macrophages). In an attempt to identify cis-elements responsible for this restricted pattern of expression, we produced transgenic mice carrying reporter genes linked to the hu...

We have previously reported that ANG II stimulation increased superoxide anion (O2-) through the activation of NAD(P)H oxidase and inhibited nitric oxide (NO)-dependent control of myocardial oxygen consumption (MVo2) by scavenging NO. Our objective was to investigate the role of NAD(P)H oxidase, especially the gp91phox subunit, in the NO-dependent control of MVo2. MVo2 in mice with defects in t...