Tissue heme oxygenase-1 exerts anti-inflammatory effects on LPS-induced pulmonary inflammation

Konrad, Franziska M.; Knausberg, Urs; Höne, R.; Ngamsri, Kristian-Christos; Reutershan, Jörg

doi:10.1038/mi.2015.39

Cited by 66 publications

(68 citation statements)

References 64 publications

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“…This corroborates previous studies that showed a reduction in the breakdown of alveolar capillary barriers in models of ALI/ARDS induced by LPS [42]. Additionally, in experimental cerebral malaria, the induction of HO-1 reduced the permeability of the blood brain barrier in PbA infected mice [16].…”

Section: Discussionsupporting

confidence: 91%

“…Increased levels of MCP-1, chemokine involved in recruiting of monocytes, neutrophils, and lymphocytes, were found in pulmonary alveolar macrophages isolated from a rat model of immune complex-mediated acute inflammatory lung injury [41]. This shows that hemin reduced the levels of inflammatory cytokines that are important in ALI/ARDS, which corroborates with previous results showing that HO-1 induction by hemin has anti-inflammatory effects in models of sepsis and LPS induced ALI/ARDS in mice [25, 42]. As an anti-inflammatory cytokine, which was increased in hemin treated animals, which were protected against endotoxic shock [43] and whose effect in ALI/ARDS was shown to be protective [44], IL-10 was not expected to be decreased in hemin treated animals in our data.…”

Section: Discussionsupporting

confidence: 86%

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Association of Heme Oxygenase 1 with Lung Protection in Malaria-Associated ALI/ARDS

Pereira

Ortolan

Sercundes

et al. 2016

Mediators of Inflammation

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Malaria is a serious disease, caused by the parasite of the genus Plasmodium, which was responsible for 440,000 deaths in 2015. Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the main clinical complications in severe malaria. The murine model DBA/2 reproduces the clinical signs of ALI/ARDS in humans, when infected with Plasmodium berghei ANKA. High levels of HO-1 were reported in cases of severe malaria. Our data indicated that the HO-1 mRNA and protein expression are increased in mice that develop malaria-associated ALI/ARDS (MA-ALI/ARDS). Additionally, the hemin, a HO-1 inducing drug, prevented mice from developing MA-ALI/ARDS when administered prior to the development of MA-ALI/ARDS in this model. Also, hemin treatment showed an amelioration of respiratory parameters in mice, high VEGF levels in the sera, and a decrease in vascular permeability in the lung, which are signs of ALI/ARDS. Therefore, the induction of HO-1 before the development of MA-ALI/ARDS could be protective. However, the increased expression of HO-1 on the onset of MA-ALI/ARDS development may represent an effort to revert the phenotype of this syndrome by the host. We therefore confirm that HO-1 inducing drugs could be used for prevention of MA-ALI/ARDS in humans.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 86%

Association of Heme Oxygenase 1 with Lung Protection in Malaria-Associated ALI/ARDS

Pereira

Ortolan

Sercundes

et al. 2016

Mediators of Inflammation

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“…They determined the main expression of the chemokine SDF-1 in the alveolar epithelium and alveolar macrophages during acute pulmonary inflammation. The predominant effect of CXCR7 on pulmonary epithelium is further supported by our findings from the chemokine assay with a significant reduction of CXCL1, which is mainly released by the pulmonary epithelium (11,14,15). The reduction of the PMN chemoattractant CXCL2/3, mainly secreted by alveolar macrophages (11), is also in line with the above-mentioned findings from Petty et al (7).…”

Section: Discussionsupporting

confidence: 80%

“…Thereby, CXCL1 is mainly released by the epithelium, and CXCL2/3 is released by alveolar macrophages and PMNs (11,14,15). LPS exposure induced the release of both chemokines after 3 and 24 h (all p , 0.05) (Fig.…”

Section: Cxcr7 Inhibition Ameliorated the Release Of Inflammatory Chementioning

confidence: 99%

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The Pivotal Role of CXCR7 in Stabilization of the Pulmonary Epithelial Barrier in Acute Pulmonary Inflammation

Ngamsri

Müller

Bösmüller

et al. 2017

The Journal of Immunology

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Acute pulmonary inflammation is still a frightening complication in intensive care units and has a high mortality. Specific treatment is not available, and many details of the pathomechanism remain unclear. The recently discovered chemokine receptor CXCR7 and its ligand stromal cell–derived factor (SDF)-1 are known to be involved in inflammation. We chose to investigate the detailed role of CXCR7 in a murine model of LPS inhalation. Inflammation increased pulmonary expression of CXCR7, and the receptor was predominantly expressed on pulmonary epithelium and on polymorphonuclear neutrophil (PMNs) after transepithelial migration into the alveolar space. Specific inhibition of CXCR7 reduced transepithelial PMN migration by affecting the expression of adhesion molecules. CXCR7 antagonism reduced the most potent PMN chemoattractants CXCL1 and CXCL2/3. After inhibiting CXCR7, NF-κB phosphorylation was reduced in lungs of mice, tight junction formation increased, and protein concentration in the bronchoalveolar lavage diminished, showing the impact of CXCR7 on stabilizing microvascular permeability. In vitro studies with human cells confirmed the pivotal role of CXCR7 in pulmonary epithelium. Immunofluorescence of human lungs confirmed our in vivo data and showed an increase of the expression of CXCR7 in pulmonary epithelium. Highlighting the clinical potential of CXCR7 antagonism, nebulization of the agent before and after the inflammation showed impressive anti-inflammatory effects. Additional CXCR7 inhibition potentiated the effect of SDF-1 antagonism, most probably by downregulating SDF-1 and the second receptor of the chemokine (CXCR4) expression. In conclusion, our data identified the pivotal role of the receptor CXCR7 in pulmonary inflammation with a predominant effect on the pulmonary epithelium and PMNs.

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Malaria, anemia, and invasive bacterial disease: A neutrophil problem?

Mooney

Galloway

Riley

2018

Journal of Leukocyte Biology

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Invasive bacterial disease is well described in immunocompromised hosts, including those with malaria infection. One bacterial infection frequently observed in children with Plasmodium falciparum infection is nontyphoidal salmonella (NTS) infection, in which a typically intestinal infection becomes systemic with serious, often fatal, consequences. In this review, we consider the role of malaria‐induced immunoregulatory responses in tipping the balance from tissue homeostasis during malaria infection to risk of invasive NTS. Also, neutrophils are crucial in the clearance of NTS but their ability to mount an oxidative burst and kill intracellular Salmonella is severely compromised during, and for some time after, an acute malaria infection. Here, we summarize the evidence linking malaria and invasive NTS infections; describe the role of neutrophils in clearing NTS infections; review evidence for neutrophil dysfunction in malaria infections; and explore roles of heme oxygenase‐1, IL‐10, and complement in mediating this dysfunction. Finally, given the epidemiological evidence that low density, subclinical malaria infections pose a risk for invasive NTS infections, we consider whether the high prevalence of such infections might underlie the very high incidence of invasive bacterial disease across much of sub‐Saharan Africa.

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Tissue heme oxygenase-1 exerts anti-inflammatory effects on LPS-induced pulmonary inflammation

Cited by 66 publications

References 64 publications

Association of Heme Oxygenase 1 with Lung Protection in Malaria-Associated ALI/ARDS

Association of Heme Oxygenase 1 with Lung Protection in Malaria-Associated ALI/ARDS

The Pivotal Role of CXCR7 in Stabilization of the Pulmonary Epithelial Barrier in Acute Pulmonary Inflammation

Malaria, anemia, and invasive bacterial disease: A neutrophil problem?

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