Interleukin-6 mediates neutrophil mobilization from bone marrow in pulmonary hypertension

Florentin, Jonathan; Zhao, Jingsi; Tai, Yi-Yin; Vasamsetti, Sathish Babu; O'Neil, Scott; Kumar, Rahul; Arunkumar, Anagha; Watson, Annie; Sembrat, John; Bullock, Grant C.; Sanders, Linda; Kassa, Biruk; Rojas, Mauricio; Graham, Brian B.; Chan, Stephen Y.; Dutta, Partha

doi:10.1038/s41423-020-00608-1

Cited by 44 publications

(32 citation statements)

References 66 publications

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“…Although our data show that Hif1a silencing decreased HSPC proliferation (Figure 4I), HIF-1⍺ also promotes inflammation. Congruently, our and other groups have shown that hypoxia results in systemic inflammation [78][79][80] . Proinflammatory cytokines can drive HSPC into the cell cycle and increase their proliferation.…”

Section: Discussionmentioning

confidence: 83%

“…Ten to twelve-week-old C57BL/6J male mice were exposed to normobaric hypoxic-10% oxygen, which represents 50% of the normal amount of oxygen, or normoxic conditions for 3 weeks. This oxygen concentration resulted in increased right ventricular systolic pressure, Fulton index and pulmonary vascular remodeling 80,81 . Of note, we have observed a very high mortality when we further decreased O2 concentration.…”

Section: Animalsmentioning

confidence: 99%

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VEGF receptor promotes hypoxia-induced hematopoietic progenitor proliferation and differentiation

Florentin

O'Neil

Vasamsetti

et al. 2021

Preprint

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Intermittent or chronic hypoxia is associated with morbidity and mortality in many diseases such as obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), respectively. We found exaggerated inflammation with heightened numbers of inflammatory leukocytes in these patients compared with age-matched controls. Chronically hypoxic mice exhibited similar trend and induced proliferation of hematopoietic stem and progenitor cells (HSPC), precursors of inflammatory leukocytes. Consistently, a transcriptomic analysis of human HSPC exposed to hypoxic conditions revealed elevated expression of genes involved in progenitor mobilization. Additionally, bone marrow cells in mice under hypoxic conditions expressed high amount of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFr) and its target genes in hypoxic conditions. In silico and ChIP experiments demonstrated that HIF-1⍺ binds to the promoter region of VEGFr. These results indicate that VEGF signaling in HSPC is an important mediator of their proliferation and differentiation in hypoxia-induced inflammation and represents a potential therapeutic target to prevent aberrant inflammation in hypoxia-associated diseases.

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Section: Discussionmentioning

confidence: 83%

Section: Animalsmentioning

confidence: 99%

VEGF receptor promotes hypoxia-induced hematopoietic progenitor proliferation and differentiation

Florentin

O'Neil

Vasamsetti

et al. 2021

Preprint

Self Cite

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“…It is widely established that people with CTD are more likely to develop group 1 PAH (9). Preclinical research supports the idea that PAH may be caused by immunological dysfunction (20). CTD-PAH is typified by vasoconstriction and modification of small-to-medium-sized pulmonary arterioles, as well as significant interstitial inflammation and fibrotic alterations (21).…”

Section: Discussionmentioning

confidence: 97%

Effect of Levosimendan on Acute Decompensated Right Heart Failure in Patients With Connective Tissue Disease-Associated Pulmonary Arterial Hypertension

Feng

Zhao

et al. 2022

Front. Med.

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AimsAcute decompensated right heart failure (RHF) in chronic precapillary pulmonary hypertension is often typified by a swiftly progressive syndrome involving systemic congestion. This results from the impairment of the right ventricular filling and/or a reduction in the flow output of the right ventricle, which has been linked to a dismal prognosis of short duration. Despite this, there are limited therapeutic data regarding these acute incidents. This study examined the effect of levosimendan on acute decompensated RHF in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH).MethodsThis retrospective study included 87 patients with confirmed CTD-PAH complicated acute decompensated RHF between November 2015 and April 2021. We collected biological, clinical, and demographic data, as well as therapy data, from patients with acute decompensated RHF who required levosimendan treatment in the cardiac care unit (CCU) for CTD-PAH. The patients were divided into two groups according to the levosimendan treatment. Patient information between the two groups was systematically compared in hospital and at follow-up.ResultsOxygen saturation of mixed venose blood (SvO2), estimated glomerular filtration rate (eGFR), 24-h urine output, and tricuspid annular plane systolic excursion (TAPSE) were found to be considerably elevated in the levosimendan cohort compared with the control cohort. Patients in the levosimendan cohort exhibited considerably reduced levels of C-reactive protein (CRP), white blood cell (WBC), troponin I, creatinine, NT-proBNP, and RV diameter compared with those in the control cohort. A higher survival rate was observed in the levosimendan cohort.ConclusionsLevosimendan treatment could effectively improve acute decompensated RHF and systemic hemodynamics in CTD-PAH patients, with positive effects on survival in hospital and can, therefore, be considered as an alternative treatment option for improving clinical short-term outcomes.

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“…Therefore, it is possible to suggest that the saliva level of IL-6 may influence neutrophil recruitment to the oral cavity as it enhances neutrophil egress ( 83 ). On the other hand, we found that Gal-9 interaction with CD44 enhances neutrophil migration in vitro .…”

Section: Discussionmentioning

confidence: 99%

Differential Signature of the Microbiome and Neutrophils in the Oral Cavity of HIV-Infected Individuals

et al. 2021

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HIV infection is associated with a wide range of changes in microbial communities and immune cell components of the oral cavity. The purpose of this study was to evaluate the oral microbiome in relationship to oral neutrophils in HIV-infected compared to healthy individuals. We evaluated oral washes and saliva samples from HIV-infected individuals (n=52) and healthy controls (n=43). Using 16S-rRNA gene sequencing, we found differential β-diversity using Principal Coordinate Analysis (PCoA) with Bray-Curtis distances. The α-diversity analysis by Faith’s, Shannon, and observed OTUs indexes indicated that the saliva samples from HIV-infected individuals harbored significantly richer bacterial communities compared to the saliva samples from healthy individuals. Notably, we observed that five species of Spirochaeta including Spirochaetaceae, Spirochaeta, Treponema, Treponema amylovorum, and Treponema azotonutricum were significantly abundant. In contrast, Helicobacter species were significantly reduced in the saliva of HIV-infected individuals. Moreover, we found a significant reduction in the frequency of oral neutrophils in the oral cavity of HIV-infected individuals, which was positively related to their CD4+ T cell count. In particular, we noted a significant decline in CD44 expressing neutrophils and the intensity of CD44 expression on oral neutrophils of HIV-infected individuals. This observation was supported by the elevation of soluble CD44 in the saliva of HIV-infected individuals. Overall, the core oral microbiome was distinguishable between HIV-infected individuals on antiretroviral therapy compared to the HIV-negative group. The observed reduction in oral neutrophils might likely be related to the low surface expression of CD44, resulting in a higher bacterial diversity and richness in HIV-infected individuals.

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Interleukin-6 mediates neutrophil mobilization from bone marrow in pulmonary hypertension

Cited by 44 publications

References 66 publications

VEGF receptor promotes hypoxia-induced hematopoietic progenitor proliferation and differentiation

VEGF receptor promotes hypoxia-induced hematopoietic progenitor proliferation and differentiation

Effect of Levosimendan on Acute Decompensated Right Heart Failure in Patients With Connective Tissue Disease-Associated Pulmonary Arterial Hypertension

Differential Signature of the Microbiome and Neutrophils in the Oral Cavity of HIV-Infected Individuals

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