Chemotactic factor‐induced generation of superoxide radicals by human neutrophils

Simchowitz, L; Mehta, J M; Spilberg, Isaias

doi:10.1002/art.1780220711

Cited by 140 publications

(86 citation statements)

References 30 publications

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“…Figure 1d shows that CEM cells used glycolysis as their main source of energy irrespective of the pO 2 in culture medium because they continuously produced lactate in normal and hypoxia conditions. However, we noticed that hypoxia increased the anaerobic glycolysis in CEM cells by significantly increasing the lactate production in the culture medium at 9 and 12 h. This is in agreement with previous observations that, after stimulation, the glucose catabolism in immune cells increased [16] and that inhibitors of glycolysis impaired the function of immune cells whereas inhibitors of oxidative phosphorylation did not [17][18][19]. Our results also fit nicely with a recent report that concludes to a role of hypoxiainduced adenosine via A 2A R in high glucose and lactate plasma levels [20].…”

Section: In Vitro Hypoxia Conditionssupporting

confidence: 92%

Fall in oxygen tension of culture medium stimulates the adenosinergic signalling of a human T cell line

Jacquin

Franceschi

et al. 2012

Purinergic Signalling

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We examined the short-course expression of various parameters involved in the adenosinergic signalling of a human T cell line during in vitro decrease of the medium culture oxygen tension mimicking in vivo hypoxia. Fall of 92 mmHg in oxygen tension of culture medium induced in CEM, a CD4+ human T cell line, a continuous production of hypoxia-inducing factor-1α with a plateau value at 9 h, a rapid increase in adenosine production peaking at 3 h and a decrease in adenosine deaminase peaking at 6 h. The adenosine A 2A receptor (A 2A R) protein level of CEM cells was enhanced with a peak at 6 h. Intracellular 3′,5′-cyclic adenosine monophosphate accumulated in CEM cells with a maximal level at 9 h. These results show that a humancultured T cells line can upregulate its own adenosine production and A 2A R expression during exposure to acute hypoxia. Hypoxia-increased stimulation of the adenosinergic signalling of T cells may have immunosuppressive properties and, consequently, A 2A R agonists may have therapeutic relevance.

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Section: In Vitro Hypoxia Conditionssupporting

confidence: 92%

Fall in oxygen tension of culture medium stimulates the adenosinergic signalling of a human T cell line

Jacquin

Franceschi

et al. 2012

Purinergic Signalling

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“…These results with sodium aurothiomalate are comparable to those previously reported by Simchowitz and colleagues in similar studies using aurothioglucose (14).…”

Section: Discussionsupporting

confidence: 92%

Effects of gold compounds on the function of phagocytic cells

Davis

Johnston

Miller

et al. 1983

Arthritis & Rheumatism

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The effect of sodium aurothiomalate and triethyl‐phosphine gold on the generation of superoxide radicals by chemotactic tripeptide‐activated polymorphonuclear leukocytes has been investigated using a cytochrome C reduction technique. Neither gold compound inhibited the binding of the tripeptide to cells. Sodium aurothiomalate in concentrations ranging from 1 to 100 μg/ml produced mild, nonsignificant inhibition of the generation of superoxide radicals. In contrast, triethylphosphine gold at a concentration of 0.25 μg/ml was associated with a mild enhancement of superoxide radical production, but the enhancement was not statistically significant. At concentrations of 1.25 μg/ml and above, there was a profound inhibition of superoxide radical production by these activated cells. Since the products of the respiratory burst, including superoxide, are thought to be inflammatory mediators, it is postulated that the inhibition of superoxide radical generation by gold compounds may be another mechanism by which the compounds modulate their antiinflammatory effects in patients with rheumatoid disease.

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“…Indeed, published data verify that PMN generate 1-2 nmoles/minute/106 cells in vitro, and that in the cavum of the knee joint, effusions of 10-20 ml containing 5,000-20,000 PMN/mm3 (equivalent to 50 x 1 O6 to 400 X lo6 PMN) are not uncommon during flares of rheumatoid arthritis (3,31,32).…”

Section: Discussionmentioning

confidence: 90%

Oxygen radicals as effectors of cartilage destruction. Direct degradative effect on matrix components and indirect action via activation of latent collagenase from polymorphonuclear leukocytes

Burkhardt

Schwingel

Menninger

et al. 1986

Arthritis & Rheumatism

153

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Degradation of intact cartilaginous tissue (bovine nasal cartilage) by oxygen‐derived free radicals (ODFR) generated enzymatically by xanthine oxidase and hypoxanthine was studied. The degree of tissue destruction was determined by measuring the indentation under a defined compression force as well as by the loss of uronic acid‐ and hydroxyproline‐containing matrix components. Cartilage slices altered by prior elastase treatment were more susceptible to oxygen radical attack than were intact tissue specimens. Degradation of cartilage matrix by ODFR was strongly inhibited by superoxide dismutase or catalase. Coincubation of latent collagenase from polymorphonuclear leukocytes with the ODFR‐generating system led to activation of collagenolytic activity, resulting in marked degradation of the bovine cartilage slices. In further studies, activated polymorphonuclear leukocyte‐collagenase was shown to degrade intact human articular cartilage to a degree of mechanical insufficiency. Thus, our assay system serves as an in vitro model of tissue damage, which may be relevant to pathophysiologic states such as rheumatoid arthritis.

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Chemotactic factor‐induced generation of superoxide radicals by human neutrophils

Abstract: Human peripheral neutrophils generated superoxide radicals as assessed by ferricytochrome C reduction in response to activation by the synthetic chemotactic factor, N-formyl-methionyl-leucyl-phenylalanine.

Cited by 140 publications

References 30 publications

Fall in oxygen tension of culture medium stimulates the adenosinergic signalling of a human T cell line

Fall in oxygen tension of culture medium stimulates the adenosinergic signalling of a human T cell line

Effects of gold compounds on the function of phagocytic cells

Oxygen radicals as effectors of cartilage destruction. Direct degradative effect on matrix components and indirect action via activation of latent collagenase from polymorphonuclear leukocytes

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