Regulation of Neutrophil Superoxide Production in Sepsis

Solomkin, Joseph S.; Cotta, Leala A.; Brodt, Julia K.; Hurst, James Willard

doi:10.1001/archsurg.1985.01390250081013

Cited by 36 publications

(15 citation statements)

References 22 publications

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“…In contradistinction to patients with CGD that we studied previously (7), patients with acute bacterial infection have normal mechanisms for generating superoxide and MPO in the resting state (30)(31)(32). Solomkin et al reported normal superoxide formation in patients with intraabdominal infections in response to FMLP but not with serum opsonized zymosan (25). We found that overall superoxide anion production was similar in resting patient and control PMN.…”

Section: Discussionsupporting

confidence: 56%

“…The microtiter plates were then incubated for 30 min at 37°C in a 5% CO2 incubator. 50 Ml of 0.2 M sodium phosphate buffer, pH 6.2, was then added followed by 25 Ml of a solution containing equal parts of 15 mM H202 combined with 3.9 mM 3'3' dimethoxybenzidine. A visible color reaction was stopped after 15 min at room temperature by 1% sodium azide.…”

Section: Methodsmentioning

confidence: 99%

“…The amount of superoxide anion generated was assayed by measurement of the reduction of ferricytochrome c (25). Assays were performed in 96-well flat bottom plates (Costar, Cambridge, MA).…”

Section: Methodsmentioning

confidence: 99%

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Studies on phagocytosis in patients with acute bacterial infections.

Simms¹,

Frank

Quinn

et al. 1989

J. Clin. Invest.

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Polymorphonuclear leukocytes (PMN) and monocytes from 20 patients with acute bacterial infections were examined for phagocytic function. PMN of patients expressed markedly enhanced phagocytosis as measured by the ingestion of erythrocyte (E)IgG and IgG/C3b-coated E. Phagocytosis of E coated with C3b alone was not seen, while low levels of ingestion of iC3b-E by patients' PMNs was noted. Monocytes from patients and controls expressed similar phagocytic activity in a fixed endpoint assay; however, the kinetics of phagocytosis by patients' monocytes was strikingly faster. Superoxide anion (02) and myeloperoxidase activities were similar to controls in PMN of four patients studied on day 1 of admission.PMN from two of three patients studied longitudinally showed an initial elevation in EIgG phagocytosis, which fell to normal levels by day 4, concomitantly with increased 0°gener-ation and clinical improvement. Phagocytosis remained elevated in the third patient who did not clear his septicemia.

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Section: Discussionsupporting

confidence: 56%

Section: Methodsmentioning

confidence: 99%

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Studies on phagocytosis in patients with acute bacterial infections.

Simms¹,

Frank

Quinn

et al. 1989

J. Clin. Invest.

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show abstract

“…The assays were performed as previously described [18], using 96-well U-shaped Immulon 1-l plates (Dynatech Labs, Chantilly, VA). PMN at 8 2 10 6 /ml were pretreated with cytochalasin B (5 g/ml) immediately before 25 l of the PMN were added to each well.…”

Section: Myeloperoxidase Releasementioning

confidence: 99%

Polymorphonuclear leucocyte (PMN)-derived inflammatory cytokines—regulation by oxygen tension and extracellular matrix

Derevianko

D’Amico

Simms

1996

Clinical and Experimental Immunology

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SUMMARYThe kinetics of IL-8, tumour necrosis factor-alpha (TNF-®) and IL-1¯release by PMN adhered to fibronectin, laminin or plastic for 24 h in response to continuous stimulation with lipopolysaccharide (LPS; 50 ng/ml), N-formyl-Met-Leu-Phe (fMLP; 100 mM), or phorbol myristate acetate (PMA; 10 ng/ml), was investigated under altered oxygen tension conditions. Cell supernatants were sampled for cytokine content every 6 h and measured by ELISA. IL-8 was the most abundant cytokine, produced in a range of up to 5 . 4 ng/ml; TNF-® and IL-1¯were produced in a range of up to 1 ng/ml. During normoxia, LPS was the most potent stimulus, inducing the release of each cytokine, while fMLP showed a less pronounced effect on IL-8 and IL-1¯production and markedly inhibited TNF-® production. PMA markedly suppressed IL-8 and IL-1¯release and failed to induce any release of TNF-®. Hypoxia had an overall inhibitory effect on cytokine release except for PMA-induced IL-1¯release, and hypoxia/reoxygenation had a significant up-regulating effect except for a further inhibition of fMLP-induced release of TNF-®. Integrin-matrix protein ligation differentiated both spontaneous and externally induced cytokine release and its sensitivity to alteration in oxygen tension. Thus the process of PMN elaboration of inflammatory cytokines is controlled on multiple levels of signal transduction, differentiated by integrin-extracellular matrix interactions, and is sensitive to alterations in microenvironmental oxygen tension.

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“…Sepsis is associated with immunoparalysis and deactivation of the innate immune system, through reduced HLA-DR expression on circulating monocytes and impaired bacterial killing by neutrophils from patients with sepsis (12)(13)(14)(15)(16). This has generated interest in targeting factors responsible for myeloid cell maturation and function in sepsis.…”

mentioning

confidence: 99%

Interleukin 5 Is Protective during Sepsis in an Eosinophil-Independent Manner

Linch

Danielson

Kelly

et al. 2012

Am J Respir Crit Care Med

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Rationale: The immune response in sepsis is characterized by overt immune dysfunction. Studies indicate immunostimulation represents a viable therapy for patients. One study suggests a potentially protective role for interleukin 5 (IL-5) in sepsis; however, the loss of eosinophils in this disease presents a paradox. Objectives: To assess the protective and eosinophil-independent effects of IL-5 in sepsis. Methods: We assessed the effects of IL-5 administration on survival, bacterial burden, and cytokine production after polymicrobial sepsis. In addition, we examined the effects on macrophage phagocytosis and survival using fluorescence microscopy and flow cytometry. Measurements and Main Results: Loss of IL-5 increased mortality and tissue damage in the lung, IL-6 and IL-10 production, and bacterial burden during sepsis. Therapeutic administration of IL-5 improved mortality in sepsis. Interestingly, IL-5 administration resulted in neutrophil recruitment in vivo. IL-5 overexpression in the absence of eosinophils resulted in decreased mortality from sepsis and increased circulating neutrophils and monocytes, suggesting their importance in the protective effects of IL-5. Furthermore, novel data demonstrate IL-5 receptor expression on neutrophils and monocytes in sepsis. IL-5 augmented cytokine secretion, activation, phagocytosis, and survival of macrophages. Importantly, macrophage depletion before the onset of sepsis eliminated IL-5-mediated protection. The protective effects of IL-5 were confirmed in humans, where IL-5 levels were elevated in patients with sepsis. Moreover, neutrophils and monocytes from patients expressed the IL-5 receptor. Conclusions: Taken together, these data support a novel role for IL-5 on noneosinophilic myeloid populations, and suggest treatment with IL-5 may be a viable therapy for sepsis.

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Regulation of Neutrophil Superoxide Production in Sepsis

Cited by 36 publications

References 22 publications

Studies on phagocytosis in patients with acute bacterial infections.

Studies on phagocytosis in patients with acute bacterial infections.

Polymorphonuclear leucocyte (PMN)-derived inflammatory cytokines—regulation by oxygen tension and extracellular matrix

Interleukin 5 Is Protective during Sepsis in an Eosinophil-Independent Manner

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