N-Acetylcysteine reduces respiratory burst but augments neutrophil phagocytosis in intensive care unit patients

Heller, A. R.; Groth, Gesine; Heller, Susanne; Breitkreutz, Raoul; Nebe, Thomas; Quintel, Michael; Koch, Thea

doi:10.1097/00003246-200102000-00009

Cited by 82 publications

(71 citation statements)

References 30 publications

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“…the production of reactive oxygen species, is an important defense mechanism by which phagocytes destroy micro-organisms (22)(23)(24). In a rat model of IgG immune complex-induced lung injury, reactive oxygen species may explain early induction of lung injury (within 30 min).…”

Section: Discussionmentioning

confidence: 99%

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Complement C5a Is a Key Mediator of Meconium-Induced Neutrophil Activation

Castellheim

Pharo

Fung³

et al. 2005

Pediatr Res

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Meconium aspiration syndrome is a serious condition of the newborn characterized by pulmonary inflammation with substantial neutrophil infiltration. We recently showed that meconium is a potent activator of complement. The aim of the present study was to investigate a possible role for complement in meconiuminduced neutrophil activation. Meconium was incubated in human whole blood anticoagulated with lepirudin, a specific thrombin inhibitor that does not affect complement activation. Complement activation was detected by measuring the terminal complement complex. Neutrophil oxidative burst and changes in CD11b and L-selectin expression were measured by flow cytometry. Complement was inhibited using the MAb 166-32 and 137-26, which block factor D and neutralize C5a, respectively. Meconium markedly activated the neutrophils, as revealed by up-regulation of CD11b, accentuation of L-selectin shedding, and induction of oxidative burst. Complement inhibition using the anti-factor D antibody completely (95-100%) blocked meconium-induced changes in CD11b and L-selectin expression, whereas oxidative burst was reduced by 60 -70%. The anti-C5a antibody inhibited the neutrophil activation to the same extent as anti-factor D. The data suggest that complement activation is largely responsible for the neutrophil inflammatory responses induced by meconium in vitro and that C5a is a key mediator of this response. Abbreviations ARDS, acute respiratory distress syndrome AU, arbitrary units DHR, dihydrorhodamine LPS, lipopolysaccharide MAS, meconium aspiration syndrome MFI, median fluorescence intensity PE, phycoerythrin PMA, phorbol-12-␤-myristat-13-␣-acetate TCC, terminal SC5b-9 complement complex Meconium aspiration syndrome (MAS) may cause a profound lung inflammation similar to acute respiratory distress syndrome (ARDS). A substantial increase in neutrophils in the airways; increased levels of inflammatory cytokines, eicosanoids, superoxide anions, and endothelin-1; expression of inducible nitric oxide synthase and cyclooxygenase-2; and activation of nuclear factor-B have been described in MAS (1-8). A profound inflammatory response and the release of leukocyte cytotoxic products have an important role in initiation and propagation of lung injury in ARDS, in which neutrophils and their cytotoxic products play a crucial role (9).The complement system is a key mediator of inflammation. Complement-mediated activation of neutrophils and monocytes leads to cytokine production; release of lipid mediators and histamine; oxidative burst; and altered expression of adhesion molecules, including increased expression of CD11b and shedding, revealed as decreased expression of CD62L. We showed recently that meconium is a potent activator of the alternative complement pathway in vitro (10). To study the interaction between all participating inflammatory systems, we used an in vitro human whole-blood model that is based on the use of lepirudin, a thrombin-specific anticoagulant that does not interfere with complement activation (11). We hypot...

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Section: Discussionmentioning

confidence: 99%

“…In contrast, it slightly but significantly increased TCC formation to 36 MFI (23-66; p Ͻ 0.05). No change in TCC formation was seen for the isotype-matched control antibody [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]]. …”

mentioning

confidence: 99%

Complement C5a Is a Key Mediator of Meconium-Induced Neutrophil Activation

Castellheim

Pharo

Fung³

et al. 2005

Pediatr Res

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“…Plasma REDST was previously shown to be correlated with the intracellular glutathione redox state, at least in some tissues, 26 and NAC treatment was previously shown to cause a decrease in the production of superoxide anion by stimulated neutrophils. [27][28][29][30] In view of recent evidence for a role of nitrosothiols in regulating the ventilatory response at the level of the nucleus tractus solitarius, 23 there is also the possibility that oral NAC application or the endogenous concentration of thiols or REDST may modulate HVR by altering nitric oxide production. and after 4 days of treatment (day 5) and the data on day 6 before, during, and after a 6-hour exposure to prolonged hypoxia indicated by the windows.…”

Section: Discussionmentioning

confidence: 99%

Effect of N-acetyl-cysteine on the hypoxic ventilatory response and erythropoietin production: linkage between plasma thiol redox state and O2 chemosensitivity

Hildebrandt

Alexander

Bärtsch

et al. 2002

Blood

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“…N-acetylcysteine has been extensively studied in critically ill patients with acute respiratory distress syndrome, organ failure, and septic shock. These studies have produced inconsistent results [83,89,90]. Crimi et al [83] suggested that larger trials in specific populations of critically ill patients in which Nacetylcysteine is administered early could potentially provide some beneficial effects.…”

Section: Antioxidant Nutrients In Neurocritical Carementioning

confidence: 99%

Antioxidant Strategies in Neurocritical Care

Hanafy

Selim

2012

Neurotherapeutics

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An increase in oxidative stress and overproduction of oxidizing reactive species plays an important role in the pathophysiology of several conditions encountered in the neurocritical care setting including: ischemic and hemorrhagic strokes, traumatic brain injury, acute respiratory distress syndrome, sepsis, and organ failure. The presence of oxidative stress in these conditions is supported by a large body of preclinical and clinical studies, and provides a rationale to support a potential therapeutic role for antioxidants. The purpose of this article is to briefly review the basic mechanisms and molecular biology of oxidative stress, summarize its role in critically ill neurological patients, and review available data regarding the potential role of antioxidant strategies in neurocritical care and future directions.

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N-Acetylcysteine reduces respiratory burst but augments neutrophil phagocytosis in intensive care unit patients

Cited by 82 publications

References 30 publications

Complement C5a Is a Key Mediator of Meconium-Induced Neutrophil Activation

Complement C5a Is a Key Mediator of Meconium-Induced Neutrophil Activation

Effect of N-acetyl-cysteine on the hypoxic ventilatory response and erythropoietin production: linkage between plasma thiol redox state and O2 chemosensitivity

Antioxidant Strategies in Neurocritical Care

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