Intravenous Immunoglobulin-Induced Neutrophil Apoptosis in the Lung during Murine Endotoxemia

Ishikawa, Michiko; Seishu, Ayumi; Kawakami, Saori; Maeshige, Noriaki; Miyoshi, Makoto; Ueda, Takahiro; Usami, Makoto; Nakao, Atsunori; Kotani, Joji

doi:10.1089/sur.2012.227

Cited by 9 publications

(7 citation statements)

References 18 publications

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“…This leads to secondary organ sequestration and lung infiltration by activated PMNs, which leads to lung injury and ARF. 25,27,28 Our results are in line with these findings, indicating that the inflammatory response is more strongly associated with ARF than with dysfunction of other organs, at each time point of the assessment. Furthermore, in agreement with previous studies, we noted that the most profound impact of inflammation on ARF was on the third day after OHCA.…”

Section: Discussionsupporting

confidence: 89%

“…26,27 Furthermore, two studies have suggested that the endothelium of the pulmonary microvasculature may play an active role in regulating the priming and de-priming of PMNs during their transit through the systemic circulation, as a 'gatekeeper' of a systemic inflammatory response. 25,27,28 In the case of global distress like PCAS, priming and activation of PMNs might overwhelm protective endogenous de-priming capacities of the lungs. According to this theory, I/R injury causes lung endothelial dysfunction and increased capillary permeability in the first stage of PCAS.…”

Section: Discussionmentioning

confidence: 99%

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Acute respiratory failure and inflammatory response after out-of-hospital cardiac arrest: results of the Post-Cardiac Arrest Syndrome (PCAS) pilot study

Czerwińska-Jelonkiewicz

Grand

Tavazzi

et al. 2020

European Heart Journal. Acute Cardiovascular Care

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Background: Although the lungs are potentially highly susceptible to post-cardiac arrest syndrome injury, the issue of acute respiratory failure after out-of-hospital cardiac arrest has not been investigated. The objectives of this analysis were to determine the prevalence of acute respiratory failure after out-of-hospital cardiac arrest, its association with post-cardiac arrest syndrome inflammatory response and to clarify its importance for early mortality. Methods: The Post-Cardiac Arrest Syndrome (PCAS) pilot study was a prospective, observational, six-centre project (Poland 2, Denmark 1, Spain 1, Italy 1, UK 1), studying patients resuscitated after out-of-hospital cardiac arrest of cardiac origin. Primary outcomes were: (a) the profile of organ failure within the first 72 hours after out-of-hospital cardiac arrest; (b) in-hospital and short-term mortality, up to 30 days of follow-up. Respiratory failure was defined using a modified version of the Berlin acute respiratory distress syndrome definition. Inflammatory response was defined using leukocytes (white blood cells), platelet count and C-reactive protein concentration. All parameters were assessed every 24 hours, from admission until 72 hours of stay. Results: Overall, 148 patients (age 62.9±15.27 years; 27.7% women) were included. Acute respiratory failure was noted in between 50 (33.8%) and 75 (50.7%) patients over the first 72 hours. In-hospital and short-term mortality was 68 (46.9%) and 72 (48.6%), respectively. Inflammation was significantly associated with the risk of acute respiratory failure, with the highest cumulative odds ratio of 748 at 72 hours (C-reactive protein 1.035 (1.001–1.070); 0.043, white blood cells 1.086 (1.039–1.136); 0.001, platelets 1.004 (1.001–1.007); <0.005). Early acute respiratory failure was related to in-hospital mortality (3.172, 95% confidence interval 1.496–6.725; 0.002) and to short-term mortality (3.335 (1.815–6.129); 0.0001). Conclusions: An inflammatory response is significantly associated with acute respiratory failure early after out-of-hospital cardiac arrest. Acute respiratory failure is associated with a worse early prognosis after out-of-hospital cardiac arrest.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Acute respiratory failure and inflammatory response after out-of-hospital cardiac arrest: results of the Post-Cardiac Arrest Syndrome (PCAS) pilot study

Czerwińska-Jelonkiewicz

Grand

Tavazzi

et al. 2020

European Heart Journal. Acute Cardiovascular Care

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“…IVIG was shown to contain Fas and Siglec-9 specific antibodies, which can induce apoptosis in human neutrophils [ 28 , 34 , 35 ]. In murine neutrophils, IVIG (supplied by the Japan Blood Products Organization, Osaka, Japan; 0.3 and 1 g/kg, administered intraperitoneally) was reported to limit inhibition of neutrophil apoptosis induced by lipopolysaccharide (LPS) stimulation, potentially by blocking LPS-mediated effects, although no direct pro-apoptotic activity of IVIG could be demonstrated [ 36 ]. We therefore examined whether F(ab’) 2 fragments induce apoptotic cell death in murine neutrophils as a potential mechanism contributing to the protective effect of IVIG during EAE development.…”

Section: Resultsmentioning

confidence: 99%

Protection from experimental autoimmune encephalomyelitis by polyclonal IgG requires adjuvant-induced inflammation

Quast

Keller

Weber

et al. 2016

J Neuroinflammation

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BackgroundIntravenous immunoglobulin (IVIG) proved to be an efficient anti-inflammatory treatment for a growing number of neuroinflammatory diseases and protects against the development of experimental autoimmune encephalomyelitis (EAE), a widely used animal model for multiple sclerosis (MS).MethodsThe clinical efficacy of IVIG and IVIG-derived F(ab’)2 fragments, generated using the streptococcal cysteine proteinase Ide-S, was evaluated in EAE induced by active immunization and by adoptive transfer of myelin-specific T cells. Frequency, phenotype, and functional characteristics of T cell subsets and myeloid cells were determined by flow cytometry. Antibody binding to microbial antigen and cytokine production by innate immune cells was assessed by ELISA.ResultsWe report that the protective effect of IVIG is lost in the adoptive transfer model of EAE and requires prophylactic administration during disease induction. IVIG-derived Fc fragments are not required for protection against EAE, since administration of F(ab’)2 fragments fully recapitulated the clinical efficacy of IVIG. F(ab’)2-treated mice showed a substantial decrease in splenic effector T cell expansion and cytokine production (GM-CSF, IFN-γ, IL-17A) 9 days after immunization. Inhibition of effector T cell responses was not associated with an increase in total numbers of Tregs but with decreased activation of innate myeloid cells such as neutrophils, monocytes, and dendritic cells. Therapeutically effective IVIG-derived F(ab’)2 fragments inhibited adjuvant-induced innate immune cell activation as determined by IL-12/23 p40 production and recognized mycobacterial antigens contained in Freund’s complete adjuvant which is required for induction of active EAE.ConclusionsOur data indicate that F(ab’)2-mediated neutralization of adjuvant contributes to the therapeutic efficacy of anti-inflammatory IgG. These findings might partly explain the discrepancy of IVIG efficacy in EAE and MS.

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“…The pulmonary endothelium plays an active role in regulating the priming of PMNs during their transit through the systemic circulation (Aoyama-Ishikawa, et al 2014, Singh, et al 2012). In the mouse model of sepsis, the pro-inflammatory milieu caused by endotoxin challenge impairs lung-mediated PMN de-priming, resulting in their accumulation, priming, release to the systemic circulation.…”

Section: Discussionmentioning

confidence: 99%

Endotoxemia induces lung-brain coupling and multi-organ injury following cerebral ischemia-reperfusion

Mai

Prifti

Rininger

et al. 2017

Experimental Neurology

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Post-ischemic neurodegeneration remains the principal cause of mortality following cardiac resuscitation. Recent studies have implicated gastrointestinal ischemia in the sepsis-like response associated with the post-cardiac arrest syndrome (PCAS). However, the extent to which the resulting low-grade endotoxemia present in up to 86% of resuscitated patients affects cerebral ischemia-reperfusion injury has not been investigated. Here we report that a single injection of low-dose lipopolysaccharide (50 μg/kg, IP) delivered after global cerebral ischemia (GCI) induces blood-brain barrier permeability, microglial activation, cortical injury, and functional decline in vivo, compared to ischemia alone. And while GCI was sufficient to induce neutrophil (PMN) activation and recruitment to the post-ischemic CNS, minimal endotoxemia exhibited synergistic effects on markers of systemic inflammation including PMN priming, lung damage, and PMN burden within the lung and other non-ischemic organs including the kidney and liver. Our findings predict that acute interventions geared towards blocking the effects of serologically occult endotoxemia in survivors of cardiac arrest will limit delayed neurodegeneration, multi-organ dysfunction and potentially other features of PCAS. This work also introduces lung-brain coupling as a novel therapeutic target with broad effects on innate immune priming and post-ischemic neurodegeneration following cardiac arrest and related cerebrovascular conditions.

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Intravenous Immunoglobulin-Induced Neutrophil Apoptosis in the Lung during Murine Endotoxemia

Abstract: A therapeutic IVIg dose can attenuate neutrophil accumulation and regulate neutrophil apoptosis in the lung during endotoxemia. It is possible that the pathways by which IVIG induces neutrophil apoptosis may differ depending on the IVIg concentration.

Cited by 9 publications

References 18 publications

Acute respiratory failure and inflammatory response after out-of-hospital cardiac arrest: results of the Post-Cardiac Arrest Syndrome (PCAS) pilot study

Acute respiratory failure and inflammatory response after out-of-hospital cardiac arrest: results of the Post-Cardiac Arrest Syndrome (PCAS) pilot study

Protection from experimental autoimmune encephalomyelitis by polyclonal IgG requires adjuvant-induced inflammation

Endotoxemia induces lung-brain coupling and multi-organ injury following cerebral ischemia-reperfusion

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