2020
DOI: 10.1136/thoraxjnl-2019-214076
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Activation of complement component 3 is associated with airways disease and pulmonary emphysema in alpha-1 antitrypsin deficiency

Abstract: IntroductionAlpha-1 antitrypsin (AAT) deficiency (AATD) is associated with early onset emphysema. The aim of this study was to investigate whether AAT binding to plasma constituents could regulate their activation, and in AATD, exploit this binding event to better understand the condition and uncover novel biomarkers of therapeutic efficacy.MethodsTo isolate AAT linker proteins, plasma samples were separated by size exclusion chromatography, followed by co-immunoprecipitation. AAT binding proteins were identif… Show more

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Cited by 30 publications
(33 citation statements)
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“…Complement C1s protein is an early component of the classical pathway and initiates the complement pathway and is reportedly associated with the degeneration of articular cartilage in RA. Meanwhile, inhibitory protein alpha 1-antitrypsin of the complement pathway inducing inflammation was upregulated in patients with RA [ 19 ]. Furthermore, alpha 1-antitrypsin inhibits thrombin activity and blood coagulation as well as inhibition of inflammation by complement pathway control, suggesting that aberrant blood coagulation initiated in RA can be attenuated through alpha 1-antitrypsin overexpression.…”
Section: Discussionmentioning
confidence: 99%
“…Complement C1s protein is an early component of the classical pathway and initiates the complement pathway and is reportedly associated with the degeneration of articular cartilage in RA. Meanwhile, inhibitory protein alpha 1-antitrypsin of the complement pathway inducing inflammation was upregulated in patients with RA [ 19 ]. Furthermore, alpha 1-antitrypsin inhibits thrombin activity and blood coagulation as well as inhibition of inflammation by complement pathway control, suggesting that aberrant blood coagulation initiated in RA can be attenuated through alpha 1-antitrypsin overexpression.…”
Section: Discussionmentioning
confidence: 99%
“… 121 , 122 , 123 In addition to its antiprotease effects, 124 , 125 AAT is a potent anti-inflammatory and immunomodulator. 126 , 127 , 128 , 129 , 130 AAT binds the potent neutrophil chemoattractant IL-8 to prevent excessive neutrophil infiltration, 127 blocks the in vivo biological effects of TNF, 126 regulates complement, 129 and inhibits ADAM-17. 127 Of particular relevance to critical illness, AAT also modulates the production and activity of several key pro-inflammatory cytokines, including the aforementioned IL-1β, IL-6, IL-8, and TNF, 65 , 123 , 126 , 127 , 131 while preserving the production of the anti-inflammatory and pro-resolution cytokine IL-10.…”
Section: The Cytokine Storm and Il-6r Blockade In Covid-19mentioning
confidence: 99%
“…87 As expected, SARS-CoV-2-infected patients with lung illness have a higher risk to progress to severe disease and die. 88 Since C3 is involved in airway disease and emphysema, 89 COPD patients with high levels of C3 and infected with SARS-CoV-2 may be more susceptible to develop a severe disease that stable COPD patients without exacerbations and treated with anti-inflammatory therapy. 90 Polycarpou et al 91 have an exciting approach to managing complement and the deleterious effect of the innate immune response in COVID-19 patients.…”
Section: Complementmentioning
confidence: 99%