Role of the neutrophil in adult respiratory distress syndrome

Windsor, Alastair; Mullen, Patrick G.; Fowler, Alpha A.; Sugerman, Harvey J.

doi:10.1002/bjs.1800800106

Cited by 252 publications

(110 citation statements)

References 111 publications

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“…Owing to impaired migration, sequestration of neutrophils also strikes organs not affected by infection (48). The lungs are particularly susceptible, and impaired lung function correlates with the intensity of neutrophil infiltrates (49,50). As previously shown, C5a and sublytic doses of TCC can stimulate production of LTB4 (27,51).…”

Section: Discussionmentioning

confidence: 95%

Combined Inhibition of Complement (C5) and CD14 Markedly Attenuates Inflammation, Thrombogenicity, and Hemodynamic Changes in Porcine Sepsis

Barratt‐Due

Thorgersen

Egge

et al. 2013

The Journal of Immunology

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Complement and the TLR family constitute two important branches of innate immunity. We previously showed attenuating effects on inflammation and thromogenicity by inhibiting the TLR coreceptor CD14 in porcine sepsis. In the present study, we explored the effect of the C5 and leukotriene B4 inhibitor Ornithodoros moubata complement inhibitor (OmCI; also known as coversin) alone and combined with anti-CD14 on the early inflammatory, hemostatic, and hemodynamic responses in porcine Escherichia coli–induced sepsis. Pigs were randomly allocated to negative controls (n = 6), positive controls (n = 8), intervention with OmCI (n = 8), or with OmCI and anti-CD14 (n = 8). OmCI ablated C5 activation and formation of the terminal complement complex and significantly decreased leukotriene B4 levels in septic pigs. Granulocyte tissue factor expression, formation of thrombin–antithrombin complexes (p < 0.001), and formation of TNF-α and IL-6 (p < 0.05) were efficiently inhibited by OmCI alone and abolished or strongly attenuated by the combination of OmCI and anti-CD14 (p < 0.001 for all). Additionally, the combined therapy attenuated the formation of plasminogen activator inhibitor-1 (p < 0.05), IL-1β, and IL-8, increased the formation of IL-10, and abolished the expression of wCD11R3 (CD11b) and the fall in neutrophil cell count (p < 0.001 for all). Finally, OmCI combined with anti-CD14 delayed increases in heart rate by 60 min (p < 0.05) and mean pulmonary artery pressure by 30 min (p < 0.01). Ex vivo studies confirmed the additional effect of combining anti-CD14 with OmCI. In conclusion, upstream inhibition of the key innate immunity molecules, C5 and CD14, is a potential broad-acting treatment regimen in sepsis as it efficiently attenuated inflammation and thrombogenicity and delayed hemodynamic changes.

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Section: Discussionmentioning

confidence: 95%

Combined Inhibition of Complement (C5) and CD14 Markedly Attenuates Inflammation, Thrombogenicity, and Hemodynamic Changes in Porcine Sepsis

Barratt‐Due

Thorgersen

Egge

et al. 2013

The Journal of Immunology

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“…Inflammatory lung tissue damage is a major cause of post-traumatic morbidity and mortality of intensive care patients. Although the mechanisms that lead to acute lung injury are not completely understood, an increased recruitment and reduced clearance of activated inflammatory cells, predominantly polymorphonuclear neutrophils (PMN) from the lungs are thought to be chief contributing factors [2].…”

Section: Introductionmentioning

confidence: 99%

“…Activated neutrophils play a central role in the damage of lung tissue in sepsis [1,2,16]. However, the mechanisms that control the lethal actions of neutrophils and diminish lung tissue damage in individuals who recover from sepsis are unknown.…”

Section: Introductionmentioning

confidence: 99%

Surface expression of HSP72 by LPS‐stimulated neutrophils facilitates γδT cell‐mediated killing

Hirsh¹,

Hashiguchi²,

Chen³

et al. 2006

Eur J Immunol

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During inflammation and sepsis, accumulation of activated neutrophils causes lung tissue damage and organ failure. Effective clearance of neutrophils reduces the risk of organ failure; however, its mechanisms are poorly understood. Because lungs are rich in cdT cells, we investigated the physiological role of these cells in the protection of lung tissue from infiltrating neutrophils. In a mouse model of sepsis, we found that the lungs of survivors contained significantly higher numbers of cdT cells than those of mice that died from sepsis. The number of cdT cells correlated inversely with the number of neutrophils in the lungs and with the degree of lung tissue damage. LPS rapidly elicited the expression of heat shock protein (HSP) 72 on the surface of human neutrophils. Inhibitors of transcription, protein synthesis, and intracellular protein transport blocked HSP72 expression, indicating that de novo synthesis is required. cdT cells targeted and rapidly killed LPS-treated neutrophils through direct cell-to-cell contact. Pre-treatment with neutralizing antibodies to HSP72 diminished neutrophil killing. Our data indicate that HSP72 expression on the cell surface predisposes inflamed neutrophils to killing by cdT cells. This intercellular exchange may allow cdT cells to resolve inflammation and limit host tissue damage during sepsis.

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“…At present, we have incomplete knowledge of the complex series of inflammatory events which leads to ARDS after trauma, although the local release of cytokines, 12 the complex interactions between platelets and circulating leucoytes with vascular endothelial cells, 13 the extravasation and degranulation of neutrophils to produce toxic products, 14 and the activation of neuroendocrine, complement, coagulative and fibrinolytic pathways, 14,15 are certainly involved. The histological findings include microvascular occlusion from fibrin and platelet aggregates and interstitial leakage of protein-and neutrophil-rich fluid, leading to diffuse alveolar damage.…”

Section: Current Theories Of the Pathophysiological Mechanismsmentioning

confidence: 99%

Current Concepts of Respiratory Insufficiency Syndromes After Fracture

Robinson

2001

The Journal of Bone and Joint Surgery. British volume

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Role of the neutrophil in adult respiratory distress syndrome

Cited by 252 publications

References 111 publications

Combined Inhibition of Complement (C5) and CD14 Markedly Attenuates Inflammation, Thrombogenicity, and Hemodynamic Changes in Porcine Sepsis

Combined Inhibition of Complement (C5) and CD14 Markedly Attenuates Inflammation, Thrombogenicity, and Hemodynamic Changes in Porcine Sepsis

Surface expression of HSP72 by LPS‐stimulated neutrophils facilitates γδT cell‐mediated killing

Current Concepts of Respiratory Insufficiency Syndromes After Fracture

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