ABSTRACT
Neutrophils and eosinophils share common hematopoietic precursors and usually diverge into distinct lineages with unique markers before being released from their hematopoietic site, which is the bone marrow (BM). However, previous studies identified an immature Ly6g(+) Il-5Rα(+) neutrophil population in mouse BM, expressing both neutrophil and eosinophil markers suggesting hematopoietic flexibility. Moreover, others have reported neutrophil populations expressing eosinophil-specific cell surface markers in tissues and altered disease states, confusing the field regarding eosinophil origins, function, and classification. Despite these reports, it is still unclear whether hematopoietic flexibility exists in human granulocytes. To answer this, we utilized single-cell RNA sequencing (scRNA-seq) and CITE-seq to profile human BM and circulating neutrophils and eosinophils at different stages of differentiation and determine whether neutrophil plasticity plays role in asthmatic inflammation. We show that immature metamyelocyte neutrophils in humans expand during severe asthmatic inflammation and express both neutrophil and eosinophil markers. We also show an increase in tri-lobed eosinophils with mixed neutrophil and eosinophil markers in allergic asthma and that IL-5 promotes differentiation of immature blood neutrophils into tri-lobed eosinophilic phenotypes suggesting a mechanism of emergency granulopoiesis to promote myeloid inflammatory or remodeling response in patients with chronic asthma. By providing insights into unexpectedly flexible granulocyte biology and demonstrating emergency hematopoiesis in asthma, our results highlight the importance of granulocyte plasticity in eosinophil development and allergic diseases.
ABSTRACT
The endothelium plays an important role in the regulation of the intracellular fluid, vascular permeability, and modulation of vascular focal tone and angiogenesis. Endothelial dysfunction is manifested by the loss of the endothelium ability to modulate physiology changes in its vascular bed, and actually it is considered a prognostic marker of coronary artery disease. The relevance of assessing endothelial dysfunction relies in that it has been observed in different pathologies like DM, dyslipidemia, hypertension, tabaquism and in immunologic diseases like antiphospholipid syndrome and systemic lupus. PET is a non invasive method that allows the absolute quantification of myocardial blood flow during rest, stress and adrenergic stimulation, which allows to asses endothelial function. Therefore PET is a useful diagnostic technique to identify patients with endothelial dysfunction, and in the assessment of its response to administered therapy, allowing an optimal control and prevention of secondary adverse events of these diseases.
Subject(s)
Atherosclerosis/diagnostic imaging , Atherosclerosis/physiopathology , Endothelium, Vascular/diagnostic imaging , Endothelium, Vascular/physiopathology , Positron-Emission Tomography , HumansABSTRACT
El endotelio juega un papel importante en la regulación del líquido intracelular, la permeabilidad vascular, en la modulación del tono vascular focal y la angiogénesis. La disfunción endotelial se manifiesta por la pérdida de la capacidad del endotelio de modular el comportamiento fisiológico del lecho vascular y actualmente se considera un marcador pronóstico de la enfermedad arterial coronaria. La relevancia de estudiar la disfunción endotelial radica en que ésta se ha observado en diversas patologías como diabetes mellitas (DM), dislipidemia, hipertensión arterial sistémica, tabaquismo o en enfermedades inmunológicas como síndrome antifosfolípido y lupus eritematoso sistémico. La Tomografía por Emisión de Positrones (PET) es un método no invasivo que permite cuantificar en términos absolutos el flujo miocárdico en reposo, esfuerzo y durante la estimulación adrenérgica, siendo considerado en la actualidad el estándar de oro para valorar la función endotelial. Por lo tanto el PET es una herramienta diagnóstica muy útil en identificar a los pacientes con disfunción endotelial y en evaluar la respuesta a la terapia administrada en enfermedades que se acompañen de ésta. Permitiendo un control óptimo y prevención de eventos adversos de estas enfermedades.
The endothelium plays an important role in the regulation of the intracellular fluid, vascular permeability, and modulation of vascular focal tone and angiogenesis. Endothelial dysfunction is manifested by the loss of the endothelium ability to modulate physiology changes in its vascular bed, and actually it is considered a prognostic marker of coronary artery disease. The relevance of assessing endothelial dysfunction relies in that it has been observed in different pathologies like DM, dyslipidemia, hypertension, tabaquism and in immunologic diseases like antiphospholipid syndrome and systemic lupus. PET is a non invasive method that allows the absolute quantification of myocardial blood flow during rest, stress and adrenergic stimulation, which allows to asses endothelial function. Therefore PET is a useful diagnostic technique to identify patients with endothelial dysfunction, and in the assessment of its response to administered therapy, allowing an optimal control and prevention of secondary adverse events of these diseases.
Subject(s)
Humans , Atherosclerosis/physiopathology , Atherosclerosis , Endothelium, Vascular/physiopathology , Endothelium, Vascular , Positron-Emission TomographyABSTRACT
It used to be thought that the consequences of coronary artery disease were final, and that the prognosis of the patient was limited to the extent of the ventricular dysfunction. This paradigm changed radically when the concept of hibernating myocardium was introduced, which states the existence of tissue that can regain contractile function after being re-vascularized. This introduced a new concept in cardiology: myocardial viability. This work presents a clear example of the importance of detecting myocardial viability in selected patients, due to the impact not only in treatment but in prognosis as well. It is also emphasized that positron emission tomography (PET) is the gold standard method to detect myocardial viability.
Subject(s)
Humans , Male , Middle Aged , Myocardial Stunning , Radiopharmaceuticals , Cardiotonic Agents , Dobutamine , Myocardial Infarction , Myocardial Infarction , Myocardial Stunning , Positron-Emission Tomography , Tissue SurvivalABSTRACT
UNLABELLED: Hypercholesterolemia prompts to endothelial dysfunction (ED) and ED predisposes to atherogenesis. ED appears early in the course of atherogenesis and it is considered a coronary artery disease (CAD) marker. OBJECTIVES: To assess endothelial function (EF) using Positron Emission Tomography (PET) in asymptomatic patients with recent dyslipidemia diagnosis and without history of ischemic heart disease and previous hypolipemiant treatment. MATERIAL AND METHODS: Fourteen asymptomatic patients with recent dyslipidemia diagnosis (< 6 months) were studied by obtaining a lipid profile, blood glucose, and a three phase 13N-ammonia PET scan: rest, cold pressor test (CPT) and pharmacologic stress with adenosine. EF was assessed by calculating the coronary flow reserve (CFR), endothelial-dependant vasodilatation index (EDVI), and coronary blood flow increase percentage in CPT (% Delta CF). RESULTS: 79% of patients with dyslipidemia had ED and all their values were lower than those previously published as normal: rest coronary flow 0.44 +/- 0.12 vs 0.57 +/- 0.147 (p = 0.002), CPT coronary flow 0.57 +/- 0.17 vs 0.88 +/- 0.26 (p = 0.001), stress coronary flow 1.24 +/- 0.05 vs 1.81 +/- 0.35 (p = 0.005), EDVI 1.28 +/- 0.25 vs 1.53 +/- 0.24 (p 0.017), CRF 2.79 +/- 0.94 vs 3.15 +/- 0.48 (p 0.198) and % Delta CF 29.08 +/- 24.62% vs 53 +/- 24.60% (p 0.022). CONCLUSIONS: Asymptomatic patients in early stages of dyslipidemia showed a greater ED prevalence that was detected by 13N-ammonia PET scan.
Subject(s)
Endothelium, Vascular/diagnostic imaging , Endothelium, Vascular/physiopathology , Hypercholesterolemia/diagnostic imaging , Hypercholesterolemia/physiopathology , Positron-Emission Tomography , Adult , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Prospective StudiesABSTRACT
At the beginning of the evaluation of Coronary Artery Disease (CAD), Coronary Multidetector Computed Tomography (MDCT) was exclusively used to detect calcified plaques in coronary arteries through the Calcium Score, whose value by itself is limited. Nowadays, thanks to the technological advancements, potential clinical applications, with this method, include detection of coronary arterial stenosis, assessment of coronary bridges, and evaluation of anomalous coronaries. The intraluminal coronary stent evaluation is not possible yet, but this might become possible with the new-generation scanners. At the moment, the published results seem to be promising, nonetheless, the enthusiasm generated by this method should be accompanied by adequate training, as well as by its validation and certification.
Subject(s)
Coronary Angiography/methods , Tomography, X-Ray Computed , Coronary Stenosis/diagnostic imaging , Coronary Vessel Anomalies/diagnostic imaging , Coronary Vessels/surgery , Humans , StentsABSTRACT
At the beginning of the evaluation of Coronary Artery Disease (CAD), Coronary Multidetector Computed Tomography (MDCT) was exclusively used to detect calcified plaques in coronary arteries through the Calcium Score, whose value by itself is limited. Nowadays, thanks to the technological advancements, potential clinical applications, with this method, include detection of coronary arterial stenosis, assessment of coronary bridges, and evaluation of anomalous coronaries. The intraluminal coronary stent evaluation is not possible yet, but this might become possible with the new-generation scanners. At the moment, the published results seem to be promising, nonetheless, the enthusiasm generated by this method should be accompanied by adequate training, as well as by its validation and certification.
Subject(s)
Humans , Coronary Angiography/methods , Tomography, X-Ray Computed , Coronary Stenosis , Coronary Vessel Anomalies , Coronary Vessels , StentsABSTRACT
Hypercholesterolemia prompts to endothelial dysfunction (ED) and ED predisposes to atherogenesis. ED appears early in the course of atherogenesis and it is considered a coronary artery disease (CAD) marker. OBJECTIVES: To assess endothelial function (EF) using Positron Emission Tomography (PET) in asymptomatic patients with recent dyslipidemia diagnosis and without history of ischemic heart disease and previous hypolipemiant treatment. MATERIAL AND METHODS: Fourteen asymptomatic patients with recent dyslipidemia diagnosis (< 6 months) were studied by obtaining a lipid profile, blood glucose, and a three phase 13N-ammonia PET scan: rest, cold pressor test (CPT) and pharmacologic stress with adenosine. EF was assessed by calculating the coronary flow reserve (CFR), endothelial-dependant vasodilatation index (EDVI), and coronary blood flow increase percentage in CPT (% Delta CF). RESULTS: 79% of patients with dyslipidemia had ED and all their values were lower than those previously published as normal: rest coronary flow 0.44 +/- 0.12 vs 0.57 +/- 0.147 (p = 0.002), CPT coronary flow 0.57 +/- 0.17 vs 0.88 +/- 0.26 (p = 0.001), stress coronary flow 1.24 +/- 0.05 vs 1.81 +/- 0.35 (p = 0.005), EDVI 1.28 +/- 0.25 vs 1.53 +/- 0.24 (p 0.017), CRF 2.79 +/- 0.94 vs 3.15 +/- 0.48 (p 0.198) and % Delta CF 29.08 +/- 24.62% vs 53 +/- 24.60% (p 0.022). Conclusions: Asymptomatic patients in early stages of dyslipidemia showed a greater ED prevalence that was detected by 13N-ammonia PET scan.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Endothelium, Vascular , Endothelium, Vascular , Hypercholesterolemia , Hypercholesterolemia , Positron-Emission Tomography , Case-Control Studies , Cross-Sectional Studies , Prospective StudiesABSTRACT
It used to be thought that the consequences of coronary artery disease were final, and that the prognosis of the patient was limited to the extent of the ventricular dysfunction. This paradigm changed radically when the concept of hibernating myocardium was introduced, which states the existence of tissue that can regain contractile function after being re-vascularized. This introduced a new concept in cardiology: myocardial viability. This work presents a clear example of the importance of detecting myocardial viability in selected patients, due to the impact not only in treatment but in prognosis as well. It is also emphasized that positron emission tomography (PET) is the gold standard method to detect myocardial viability.
