scholarly journals High expression of neutrophil and monocyte CD64 with simultaneous lack of upregulation of adhesion receptors CD11b, CD162, CD15, CD65 on neutrophils in severe COVID-19

2021 ◽  
Vol 8 ◽  
pp. 204993612110340
Author(s):  
Malgorzata Karawajczyk ◽  
Lena Douhan Håkansson ◽  
Miklos Lipcsey ◽  
Michael Hultström ◽  
Karlis Pauksens ◽  
...  
Keyword(s):  
Adhesion Molecules ◽  
Mean Fluorescence Intensity ◽  
Immune Dysfunction ◽  
Severe Form ◽  
Receptor Expression ◽  
Future Research ◽  
Early Biomarkers ◽  
Severe Stage ◽  
Activated Neutrophils ◽  
Edta Blood

Background and Aims: The pronounced neutrophilia observed in patients with coronavirus disease 2019 (COVID-19) infections suggests a role for these leukocytes in the pathology of the disease. Monocyte and neutrophil expression of CD64 and CD11b have been reported as early biomarkers to detect infections. The aim of this study was to study the expression of receptors for IgG (CD64) and adhesion molecules (CD11b, CD15s, CD65, CD162, CD66b) on neutrophils and monocytes in patients with severe COVID-19 after admission to an intensive care unit (ICU). Methods: The expression of receptors was analyzed using flow cytometry. EDTA blood from 23 patients with confirmed COVID-19 infection was sampled within 48 h of admission to the ICU. Leukocytes were labeled with antibodies to CD11b, CD15s, CD65s, CD162, CD64, and CD66b. Expression of receptors was reported as mean fluorescence intensity (MFI) or the percentage of cells expressing receptors. Results: Results are presented as comparison of COVID-19 patients with the healthy group and the receptor expression as MFI. Neutrophil receptors CD64 (2.5 versus 0.5) and CD66b (44.5 versus 34) were increased and CD15 decreased (21.6 versus 28.3) when CD65 (6.6 versus 4.4), CD162 (21.3 versus 21.1) and CD11b (10.5 versus 12) were in the same range. Monocytes receptors CD64 (30.5 versus 16.6), CD11b (18.7 versus 9.8), and CD162 (38.6 versus 36.5) were increased and CD15 decreased (10.3 versus 17.9); CD65 were in the same range (2.3 versus 1.96). Conclusion: Monocytes and neutrophils are activated during severe COVID-19 infection as shown by strong upregulation of CD64. High monocyte and neutrophil CD64 can be an indicator of a severe form of COVID19. The adhesion molecules (CD11b, CD162, CD65, and CD15) are not upregulated on otherwise activated neutrophils, which might lead to relative impairment of tissue migration. Low adhesion profile of neutrophils suggests immune dysfunction of neutrophils. Monocytes maintain upregulation of some adhesion molecules (CD11b, CD162) suggesting the persistence of an increased ability to migrate into tissues, even during a severe stage of COVID-19. Future research should focus on CD64 and CD11b kinetics in the context of prognosis.

scholarly journals The gut microbiome: an under-recognised contributor to the COVID-19 pandemic?

2020 ◽  
Vol 13 ◽  
pp. 175628482097491
Author(s):  
Jonathan P. Segal ◽  
Joyce W. Y. Mak ◽  
Benjamin H. Mullish ◽  
James L. Alexander ◽  
Siew C. Ng ◽  
...  
Keyword(s):  
Risk Factors ◽  
Gut Microbiome ◽  
Social Impact ◽  
Severe Disease ◽  
Receptor Expression ◽  
Attractive Potential ◽  
Future Research ◽  
Clinical Activity ◽  
Disease Course ◽  
Novel Coronavirus

The novel coronavirus infection (COVID-19) caused by the SARS-CoV-2 virus has spread rapidly across the globe, culminating in major global morbidity and mortality. As such, there has been a rapid escalation in scientific and clinical activity aimed at increasing our comprehension of this virus. This volume of work has led to early insights into risk factors associated with severity of disease, and mechanisms that underpin the virulence and dynamics involved in viral transmission. These insights ultimately may help guide potential therapeutics to reduce the human, economic and social impact of this pandemic. Importantly, the gastrointestinal (GI) tract has emerged as an important organ influencing propensity to, and potentially severity of, COVID-19 infection. Furthermore, the gut microbiome has been linked to a variety of risk factors for COVID-19 infection, and manipulation of the gut microbiome is an attractive potential therapeutic target for a number of diseases. While data profiling the gut microbiome in COVID-19 infection to date are limited, they support the possibility of several routes of interaction between COVID-19, the gut microbiome, angiotensin converting enzyme 2 (ACE-2) expression in the small bowel and colon and gut inflammation. This article will explore the evidence that implicates the gut microbiome as a contributing factor to the pathogenesis, severity and disease course of COVID-19, and speculate about the gut microbiome’s capability as a therapeutic avenue against COVID-19. Lay summary It has been noted that certain baseline gut profiles of COVID-19 patients are associated with a more severe disease course, and the gut microbiome impacts the disease course of several contributory risk factors to the severity of COVID-19. A protein called ACE-2, which is found in the small intestine among other sites, is a key receptor for COVID-19 virus entry; there is evidence that the gut microbiome influences ACE-2 receptor expression, and hence may play a role in influencing COVID-19 infectivity and disease severity. Furthermore, the gut microbiome plays a significant role in immune regulation, and hence may be pivotal in influencing the immune response to COVID-19. In terms of understanding COVID-19 treatments, the gut microbiome is known to interact with several drug classes being used to target COVID-19 and should be factored into our understanding of how patients respond to treatment. Importantly, our understanding of the role of the gut microbiome in COVID-19 infection remains in its infancy, but future research may potentially aid our mechanistic understanding of viral infection, and new ways in which we might approach treating it.

scholarly journals G protein-coupled receptor trafficking and signaling: new insights into the enteric nervous system

2019 ◽  
Vol 316 (4) ◽  
pp. G446-G452 ◽  
Author(s):  
Simona E. Carbone ◽  
Nicholas A. Veldhuis ◽  
Arisbel B. Gondin ◽  
Daniel P. Poole
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
G Protein ◽  
Molecular Mechanisms ◽  
Intestinal Inflammation ◽  
Receptor Expression ◽  
Enteric Neurons ◽  
Future Research ◽  
Detailed Knowledge ◽  
G Protein Coupled

G protein-coupled receptors (GPCRs) are essential for the neurogenic control of gastrointestinal (GI) function and are important and emerging therapeutic targets in the gut. Detailed knowledge of both the distribution and functional expression of GPCRs in the enteric nervous system (ENS) is critical toward advancing our understanding of how these receptors contribute to GI function during physiological and pathophysiological states. Equally important, but less well defined, is the complex relationship between receptor expression, ligand binding, signaling, and trafficking within enteric neurons. Neuronal GPCRs are internalized following exposure to agonists and under pathological conditions, such as intestinal inflammation. However, the relationship between the intracellular distribution of GPCRs and their signaling outputs in this setting remains a “black box”. This review will briefly summarize current knowledge of agonist-evoked GPCR trafficking and location-specific signaling in the ENS and identifies key areas where future research could be focused. Greater understanding of the cellular and molecular mechanisms involved in regulating GPCR signaling in the ENS will provide new insights into GI function and may open novel avenues for therapeutic targeting of GPCRs for the treatment of digestive disorders.

Bone Morphogenetic Proteins and Their Receptors in the Eye

2007 ◽  
Vol 232 (8) ◽  
pp. 979-992 ◽  
Author(s):  
Robert J. Wordinger ◽  
Abbot F. Clark
Keyword(s):  
Growth Factor ◽  
Bone Morphogenetic Proteins ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Bmp Signaling ◽  
Receptor Expression ◽  
Future Research ◽  
Cellular Functions ◽  
Ocular Tissues ◽  
Bmp Receptors

The human genome encodes at least 42 different members of the transforming growth factor-β superfamily of growth factors. Bone morphogenetic proteins (BMPs) are the largest subfamily of proteins within the transforming growth factor-β superfamily and are involved in numerous cellular functions including development, morphogenesis, cell proliferation, apoptosis, and extracellular matrix synthesis. This article first reviews BMPs and BMP receptors, BMP signaling pathways, and mechanisms controlling BMP signaling. Second, we review BMP and BMP receptor expression during embryonic ocular development/ differentiation and in adult ocular tissues. Lastly, future research directions with respect to BMP, BMP receptors, and ocular tissues are suggested.

scholarly journals Molecular actions of vitamin D in reproductive cell biology

Reproduction ◽  
2017 ◽  
Vol 153 (1) ◽  
pp. R29-R42 ◽  
Author(s):  
Kevin N Keane ◽  
Vinicius F Cruzat ◽  
Emily K Calton ◽  
Prue H Hart ◽  
Mario J Soares ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cell Biology ◽  
Reproductive Medicine ◽  
Reproductive Tract ◽  
Inflammatory Diseases ◽  
Hormone Secretion ◽  
Receptor Expression ◽  
Calcium Handling ◽  
Future Research ◽  
The Impact

Vitamin D (VitD) is an important secosteroid and has attracted attention in several areas of research due to common VitD deficiency in the population, and its potential to regulate molecular pathways related to chronic and inflammatory diseases. VitD metabolites and the VitD receptor (VDR) influence many tissues including those of the reproductive system. VDR expression has been demonstrated in various cell types of the male reproductive tract, including spermatozoa and germ cells, and in female reproductive tissues including the ovaries, placenta and endometrium. However, the molecular role of VitD signalling and metabolism in reproductive function have not been fully established. Consequently, the aim of this work is to review current metabolic and molecular aspects of the VitD–VDR axis in reproductive medicine and to propose the direction of future research. Specifically, the influence of VitD on sperm motility, calcium handling, capacitation, acrosin reaction and lipid metabolism is examined. In addition, we will also discuss the effect of VitD on sex hormone secretion and receptor expression in primary granulosa cells, along with the impact on cytokine production in trophoblast cells. The review concludes with a discussion of the recent developments in VitD–VDR signalling specifically related to altered cellular bioenergetics, which is an emerging concept in the field of reproductive medicine.

scholarly journals Rosiglitazone Influences the Expression of Leukocyte Adhesion Molecules and CD14 Receptor in Type 2 Diabetes Mellitus Patients

2014 ◽  
pp. S293-S298 ◽  
Author(s):  
T. ŠTULC ◽  
H. SVOBODOVÁ ◽  
Z. KRUPIČKOVÁ ◽  
R. DOLEŽALOVÁ ◽  
I. MARINOV ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Adhesion Molecules ◽  
Leukocyte Adhesion ◽  
Surface Expression ◽  
Receptor Expression ◽  
Rosiglitazone Treatment ◽  
Leukocyte Adhesion Molecules

Diabetes mellitus is associated with increased inflammatory response, which may contribute to atherosclerosis progression. Experimental results demonstrated anti-inflammatory activity of glitazones; their effect on leukocyte adhesion molecules has not been studied to date. We therefore studied the effect of rosiglitazone treatment on leukocyte surface expression of adhesion molecules in patients with type 2 diabetes mellitus and compared our results with findings in healthy subjects. 33 subjects with type 2 diabetes and 32 healthy controls were included; patients were examined at baseline and after 5 months of rosiglitazone treatment (4 mg/d). Leukocyte expression of adhesion molecules LFA-1, CD18 and ICAM-1 was quantified using flow cytometry; in addition, CD14 (lipopolysaccharide receptor) expression was analyzed as a marker of nonspecific immunity. The expression of examined molecules at baseline was higher in patients compared to controls. Despite only mild decrease in blood glucose, rosiglitazone treatment induced substantial decrease of CD18 and CD14 expression and borderline decrease of LFA-1 and ICAM-1 expression (on monocytes only). We thus observed improvement in the expression of leukocyte inflammatory markers after rosiglitazone treatment. This effect is supposed to be mediated by direct effect of rosiglitazone on PPAR-γ receptors on leukocytes.

scholarly journals NK Cell Subpopulations and Receptor Expression in Recovering SARS-CoV-2 Infection

2021 ◽  
Author(s):  
Marina Saresella ◽  
Daria Trabattoni ◽  
Ivana Marventano ◽  
Federica Piancone ◽  
Francesca La Rosa ◽  
...  
Keyword(s):  
Nk Cell ◽  
Severe Form ◽  
Cytolytic Activity ◽  
Receptor Expression ◽  
Nk Activity ◽  
Inhibitory Receptor ◽  
Inhibitory Receptors ◽  
Neurological Conditions ◽  
Cell Subpopulations ◽  
Excessive Inflammatory Response

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the pandemic of coronavirus disease (COVID-19). Whereas in most cases COVID-19 is asymptomatic or pauci symptomatic, extremely severe clinical forms are observed. In this case complex immune dysregulations and an excessive inflammatory response are observed and are the main cause of morbidity and mortality. Natural Killer cells are key players in the control of viral infection and their activity is regulated by a tight balance between activating and inhibitory receptors; an alteration of NK activity was suggested to be associated with the development of severe forms of COVID-19. In this study we analyzed peripheral NK cell subpopulations and the expression of activating and inhibitory receptors in 30 in-patients suffering from chronic neurological conditions who recovered from mild, moderate or severe SARS-CoV-2 infection comparing the results to those of 10 SARS-CoV-2-uninfected patients. Results showed that an expansion of NK subset with lower cytolytic activity and an augmented expression of the 2DL1 inhibitory receptor, particularly when in association with the C2 ligand (KIR2DL1-C2), characterized the immunological scenario of severe COVID-19 infection; an increase of NK expressing the ILT2 inhibitory receptor was instead seen in patients recovering from mild or moderate infection compared to controls. Results herein suggest that the KIR2DL1-C2 NK inhibitory complex is a risk factor toward the development of severe form of COVID-19. Our results confirm that a complex alteration of NK activity is present in COVID-19 infection and offer a molecular explanation for this observation.

The immune response in trichloroethylene hypersensitivity syndrome: A review

2017 ◽  
Vol 33 (11) ◽  
pp. 876-883 ◽  
Author(s):  
Jia-xiang Zhang ◽  
Na Li ◽  
Hui Wang ◽  
Tong Shen ◽  
Qi-xing Zhu
Keyword(s):  
Immune Dysfunction ◽  
Hypersensitivity Syndrome ◽  
Skin Lesions ◽  
Organ Injury ◽  
Future Research ◽  
Organic Substances ◽  
Research Directions ◽  
Type Iv ◽  
Liver And Kidney ◽  
Future Research Directions

Trichloroethylene (TCE) has been used for a variety of industrial and consumer cleaning purposes because of its ability to dissolve organic substances. The multisystem injuries include those of skin, liver, and kidney, which are defined as TCE hypersensitivity syndrome (THS). THS is a serious occupational health issue. However, the mechanism of immune dysfunction leading to organ injury is poorly understood. Many studies reveal that skin lesions and organ injury caused by TCE are consistent with type IV hypersensitivity, also called delayed hypersensitivity, mediated by T cells. However, many researchers found T cell-mediated type IV hypersensitivity could not account for the pathogenesis of THS fully. Humoral immunity, including immunoglobulins and complement activation, may also play a possible role in THS pathogenesis. This review will describe the history, current understanding, and future research directions of the mechanism of THS.

scholarly journals Direct Pro-Inflammatory Effect of C-Reactive Protein on Human Pulmonary Artery Endothelial Cells

2012 ◽  
Vol 10 (3) ◽  
pp. 357-363 ◽  
Author(s):  
H.J. Parekh ◽  
H.B. Nguyen ◽  
S.L. Hall ◽  
M. Rehage ◽  
J. Anholm ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Fluorescence Intensity ◽  
Mean Fluorescence Intensity ◽  
Pulmonary Vasculature ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Human Pulmonary Artery

C-reactive protein (CRP) has a prognostic role in cardiovascular and pulmonary diseases. Recent data suggest its pro-inflammatory effects in atherosclerotic lesion formation. This raises the hypothesis of whether or not CRP has pro-inflammatory effects on pulmonary vasculature by inducing the production of endothelin-1 (ET)-1, a potent vasoconstrictor and proliferative cytokine, and expression of adhesion molecules which could culminate in inflammatory cell recruitment and vascular injury. Human pulmonary artery endothelial cells (HPAECs) were cultured and incubated with 25μg/ml of human recombinant CRP and with interleukin (IL)-1β 10ng/ml, a well-known activator of endothelial cells, which served as a positive control for 24 hours. Expression of vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 was assessed by flow cytometry. Secretion of ET-1 from HPAECs was also evaluated. In this study we show that incubation of HPAECs with human recombinant CRP for 24 hours induced a significant increase in ICAM-1 expression (from 610 to 6553 mean fluorescence intensity, p < 0.005) and VCAM-1 expression (from 212 to 303 mean fluorescence intensity, p < 0.05), as compared to control. Adhesion molecule induction was similar to that observed in endothelial cells activated with IL-1β. Likewise, CRP potentiated the ET-1 production by HPAECs. The levels of ET-1 were significantly higher at 24 hours (control 19.94±3 vs CRP 46.54±18 pg/ml, p < 0.05). In conclusion, this study makes a novel observation that CRP induces expression of adhesion molecules and secretion of ET-1 in HPAECs. Our study provides the first evidence that CRP exerts direct proinflammatory effects on pulmonary artery endothelial cells.

scholarly journals 40 Years of Oxalobacter formigenes , a Gutsy Oxalate-Degrading Specialist

2021 ◽  
Author(s):  
Steven L. Daniel ◽  
Luke Moradi ◽  
Henry Paiste ◽  
Kyle D. Wood ◽  
Dean G. Assimos ◽  
...  
Keyword(s):  
Calcium Oxalate ◽  
Kidney Stone ◽  
Critical Role ◽  
Primary Hyperoxaluria ◽  
Severe Form ◽  
Stone Disease ◽  
Future Research ◽  
Oxalobacter Formigenes ◽  
Kidney Stone Disease ◽  
Degrading Bacterium

Oxalobacter formigenes , a unique anaerobic bacterium that relies solely on oxalate for growth, is a key oxalate-degrading bacterium in the mammalian intestinal tract. Degradation of oxalate in the gut by O. formigenes plays a critical role in preventing renal toxicity in animals that feed on oxalate-rich plants. The role of O. formigenes in reducing the risk of calcium oxalate kidney stone disease and oxalate nephropathy in humans is less clear, in part due to difficulties in culturing this organism, and the lack of studies which have utilized diets controlled in their content of oxalate. Herein, we review the literature on the 40 th anniversary of the discovery of O. formigenes , with a focus on its biology, its role in gut oxalate metabolism and calcium oxalate kidney stone disease, and potential areas of future research. Results from ongoing clinical trials utilizing O. formigenes in healthy volunteers and in patients with Primary Hyperoxaluria Type 1 (PH1), a rare but severe form of calcium oxalate kidney stone disease, will also be discussed. Information has been consolidated on O. formigenes strains and best practices to culture this bacterium, which should serve as a good resource for researchers.

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