Exudate Macrophages Attenuate Lung Injury by the Release of IL-1 Receptor Antagonist in Gram-negative Pneumonia

Herold, Susanne; Tabar, Tannaz Shafiei; Janßen, Hermann; Hoegner, Katrin; Cabanski, Maciej; Landgraf, Peter; Albrecht, Jens; Driever, Frank; Vadász, István; Seeger, Werner; Steinmueller, Mirko; Lohmeyer, Juergen

doi:10.1164/rccm.201009-1431oc

Cited by 96 publications

(92 citation statements)

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“…5,[35][36][37] Recent studies have identified a regulatory protective role for inflammatory monocytes in infectious diseases as they synthetize and secrete anti-inflammatory mediators, such as IL-1ra and prostaglandin E2. 8,9 However, the specific contribution of inflammatory monocytes to the regulation of inflammation in early phases of sepsis remains unclear. Our results have unveiled a key role these monocytes play in renal tissue protection via a CX3CR1-dependent adhesion of inflammatory monocytes to the renal vascular endothelium.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that inflammatory monocytes are involved in controlling inflammation in gram-negative pneumonia and abdominal infections. 8,9,[38][39][40][41][42] A lower number of inflammatory monocytes has been associated with increased lesions in the lung and in the intestinal lamina propria. 8,9,38,41 Other studies have shown that the CX3CR1/ CX3CL1 axis is involved in the pathogenesis of sepsis.…”

Section: Discussionmentioning

confidence: 99%

“…11 Recent studies have called attention to the dual role of inflammatory monocytes in acute inflammation and especially infection. They protect tissues during infectious processes, such as pneumonia or gastrointestinal toxoplasmosis, notably via their secretion of IL-1 receptor antagonist 9,12,13 (IL-1ra) or prostaglandin E2. 8 Essential crosstalk among monocytes, neutrophils, and tissue (especially epithelial cells) controls the equilibrium between inflammatory and anti-inflammatory processes.…”

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confidence: 99%

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Ly6Chigh Monocytes Protect against Kidney Damage during Sepsis via a CX3CR1-Dependent Adhesion Mechanism

Chousterman

Boissonnas

Poupel

et al. 2016

Journal of the American Society of Nephrology

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Monocytes have a crucial role in both proinflammatory and anti-inflammatory phenomena occurring during sepsis. Monocyte recruitment and activation are orchestrated by the chemokine receptors CX3CR1 and CCR2 and their cognate ligands. However, little is known about the roles of these cells and chemokines during the acute phase of inflammation in sepsis. Using intravital microscopy in a murine model of polymicrobial sepsis, we showed that inflammatory Ly6C high monocytes infiltrated kidneys, exhibited altered motility, and adhered strongly to the renal vascular wall in a chemokine receptor CX3CR1-dependent manner. Adoptive transfer of Cx3cr1-proficient monocyte-enriched bone marrow cells into septic Cx3cr1-depleted mice prevented kidney damage and promoted mouse survival. Modulation of CX3CR1 activation in septic mice controlled monocyte adhesion, regulated proinflammatory and anti-inflammatory cytokine expression, and was associated with the extent of kidney lesions such that the number of lesions decreased when CX3CR1 activity increased. Consistent with these results, the pro-adhesive I249 CX3CR1 allele in humans was associated with a lower incidence of AKI in patients with sepsis. These data show that inflammatory monocytes have a protective effect during sepsis via a CX3CR1-dependent adhesion mechanism. This receptor might be a new therapeutic target for kidney injury during sepsis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Ly6Chigh Monocytes Protect against Kidney Damage during Sepsis via a CX3CR1-Dependent Adhesion Mechanism

Chousterman

Boissonnas

Poupel

et al. 2016

Journal of the American Society of Nephrology

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“…M2-polarised macrophages have been associated with tissue repair of the acutely inflamed lung [153]; however, experimental evidence of a similar role in respiratory viral disease is limited. Monocyte-derived alveolar macrophages were found to secrete hepatocyte growth factor (HGF), a potent lung epithelial cell mitogen, which induced proliferation of type II alveolar epithelial cells in a mouse IAV infection model [154,155].…”

Section: Resolution Of Lung Injury and Alveolar Regenerationmentioning

confidence: 99%

Influenza virus-induced lung injury: pathogenesis and implications for treatment

et al. 2015

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The influenza viruses are some of the most important human pathogens, causing substantial seasonal and pandemic morbidity and mortality. In humans, infection of the lower respiratory tract of can result in flooding of the alveolar compartment, development of acute respiratory distress syndrome and death from respiratory failure. Influenza-mediated damage of the airway, alveolar epithelium and alveolar endothelium results from a combination of: 1) intrinsic viral pathogenicity, attributable to its tropism for host airway and alveolar epithelial cells; and 2) a robust host innate immune response, which, while contributing to viral clearance, can worsen the severity of lung injury. In this review, we summarise the molecular events at the virus-host interface during influenza virus infection, highlighting some of the important cellular responses. We discuss immune-mediated viral clearance, the mechanisms promoting or perpetuating lung injury, lung regeneration after influenza-induced injury, and recent advances in influenza prevention and therapy. @ERSpublications We discuss novel aspects of virus-and immune-mediated lung injury and repair after influenza infection

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“…Consistent with the proinflammatory profile of airway casts was increased IL-1b, a recruiter of macrophages, and the associated increase in IL-1 receptor antagonist (23)(24)(25). In the context of cell death, elevated levels of IL-1a (see Figures E5 and E6), a cytokine that has a functional role in the nucleus in addition to its receptormediated actions, have been shown to be associated with cell necrosis rather than apoptosis (26).…”

Section: Cytokine Profile Of Plastic Bronchitis Casts Is Proinflammatorymentioning

confidence: 53%

Immunophenotyping and Protein Profiling of Fontan-associated Plastic Bronchitis Airway Casts

et al. 2013

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Rationale: Plastic bronchitis (PB) is a rare and deadly condition that is characterized by the formation of airway casts. It most frequently occurs in children with underlying congenital heart disease that has been surgically palliated by the Fontan procedure. The Fontan circulation results in above-normal central venous pressure, and it has been hypothesized that the formation of airway casts is due to lymph leak. Knowledge of plastic bronchitis pathogenesis is poor and stems mostly from published case reports.Objectives: To garner information about cast pathogenesis by characterizing inflammatory cell phenotypes in existing formalin-preserved, paraffin-embedded samples and generating protein and cytokine-chemokine profiles of airway cast homogenates.Methods: We used immunofluorescence confocal microscopy, state-of-the-science proteomics, and a cytokine array assay to immunophenotype cellular content and to generate protein and cytokine profiles of plastic bronchitis airway casts, respectively.Measurements and Main Results: Neutrophils, eosinophils, macrophages, and B lymphocytes were identified in cast samples; there were notably fewer T lymphocytes. Fibrin(ogen) was an abundant protein in the cast proteome. Histone H4 was also abundant, and immunofluorescence microscopy demonstrated it to be mostly extracellular. The cytokine profile of plastic bronchitis casts was proinflammatory.Conclusions: Plastic bronchitis airway casts from children with Fontan physiology are composed of fibrin and are cellular and inflammatory in nature, providing evidence that their formation cannot be explained simply by lymph leak into the airways. Consequences of cellular necrosis including extracellular histones and the apparent low number of T cells indicate that a derangement in inflammation resolution likely contributes to cast formation.

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Exudate Macrophages Attenuate Lung Injury by the Release of IL-1 Receptor Antagonist in Gram-negative Pneumonia

Abstract: We conclude that recruited lung macrophages attenuate IL-1β-mediated acute lung injury in gram-negative pneumonia by release of IL-1ra.

Cited by 96 publications

References 50 publications

Ly6Chigh Monocytes Protect against Kidney Damage during Sepsis via a CX3CR1-Dependent Adhesion Mechanism

Ly6Chigh Monocytes Protect against Kidney Damage during Sepsis via a CX3CR1-Dependent Adhesion Mechanism

Influenza virus-induced lung injury: pathogenesis and implications for treatment

Immunophenotyping and Protein Profiling of Fontan-associated Plastic Bronchitis Airway Casts

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