scholarly journals The Emerging Role of Neutrophils in the Pathogenesis of Thrombosis in COVID-19

2021 ◽  
Vol 22 (10) ◽  
pp. 5368
Author(s):  
Valeria Iliadi ◽  
Ina Konstantinidou ◽  
Konstantina Aftzoglou ◽  
Sergios Iliadis ◽  
Theocharis G. Konstantinidis ◽  
...  
Keyword(s):  
Blood Cells ◽  
Recent Progress ◽  
Cell Damage ◽  
White Blood Cells ◽  
Mortality Rates ◽  
Neutrophil Extracellular Trap ◽  
High Morbidity ◽  
Infection Site ◽  
Thrombotic Complications

Previous studies have shown that COVID-19 leads to thrombotic complications, which have been associated with high morbidity and mortality rates. Neutrophils are the largest population of white blood cells and play a pivotal role in innate immunity. During an infection, neutrophils migrate from circulation to the infection site, contributing to killing pathogens. This mechanism is regulated by chemokines such as IL-8. Moreover, it was shown that neutrophils play an important role in thromboinflammation. Through a diverse repertoire of mechanisms, neutrophils, apart from directly killing pathogens, are able to activate the formation of thrombi. In COVID-19 patients, neutrophil activation promotes neutrophil extracellular trap (NET) formation, platelet aggregation, and cell damage. Furthermore, neutrophils participate in the pathogenesis of endothelitis. Overall, this review summarizes recent progress in research on the pathogenesis of COVID-19, highlighting the role of the prothrombotic action of neutrophils in NET formation.

scholarly journals Interferon and Granulopoiesis Signatures in Systemic Lupus Erythematosus Blood

2003 ◽  
Vol 197 (6) ◽  
pp. 711-723 ◽  
Author(s):  
Lynda Bennett ◽  
A. Karolina Palucka ◽  
Edsel Arce ◽  
Victoria Cantrell ◽  
Josef Borvak ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Blood Cells ◽  
White Blood Cells ◽  
Gene Expression Pattern ◽  
Formyl Peptide Receptor ◽  
High Dose ◽  
High Morbidity ◽  
Systemic Lupus

Systemic lupus erythematosus (SLE) is a prototype systemic autoimmune disease characterized by flares of high morbidity. Using oligonucleotide microarrays, we now show that active SLE can be distinguished by a remarkably homogeneous gene expression pattern with overexpression of granulopoiesis-related and interferon (IFN)-induced genes. Using the most stringent statistical analysis (Bonferroni correction), 15 genes were found highly up-regulated in SLE patients, 14 of which are targets of IFN and one, defensin DEFA-3, a major product of immature granulocytes. A more liberal correction (Benjamini and Hochberg correction) yielded 18 additional genes, 12 of which are IFN-regulated and 4 granulocyte-specific. Indeed immature neutrophils were identified in a large fraction of SLE patients white blood cells. High dose glucocorticoids, a standard treatment of disease flares, shuts down the interferon signature, further supporting the role of this cytokine in SLE. The expression of 10 genes correlated with disease activity according to the SLEDAI. The most striking correlation (P < 0.001, r = 0.55) was found with the formyl peptide receptor-like 1 protein that mediates chemotactic activities of defensins. Therefore, while the IFN signature confirms the central role of this cytokine in SLE, microarray analysis of blood cells reveals that immature granulocytes may be involved in SLE pathogenesis.

scholarly journals The Enigma of Eosinophil Degranulation

2021 ◽  
Vol 22 (13) ◽  
pp. 7091
Author(s):  
Timothée Fettrelet ◽  
Lea Gigon ◽  
Alexander Karaulov ◽  
Shida Yousefi ◽  
Hans-Uwe Simon
Keyword(s):  
Blood Cells ◽  
Inflammatory Diseases ◽  
White Blood Cells ◽  
Exact Role ◽  
Effector Cells ◽  
Effector Functions ◽  
Cytotoxic Effector ◽  
Eosinophil Degranulation

Eosinophils are specialized white blood cells, which are involved in the pathology of diverse allergic and nonallergic inflammatory diseases. Eosinophils are traditionally known as cytotoxic effector cells but have been suggested to additionally play a role in immunomodulation and maintenance of homeostasis. The exact role of these granule-containing leukocytes in health and diseases is still a matter of debate. Degranulation is one of the key effector functions of eosinophils in response to diverse stimuli. The different degranulation patterns occurring in eosinophils (piecemeal degranulation, exocytosis and cytolysis) have been extensively studied in the last few years. However, the exact mechanism of the diverse degranulation types remains unknown and is still under investigation. In this review, we focus on recent findings and highlight the diversity of stimulation and methods used to evaluate eosinophil degranulation.

Candida albicans Shunt Infection: Report of Two Cases

Neurosurgery ◽  
1986 ◽  
Vol 19 (1) ◽  
pp. 111-113 ◽  
Author(s):  
David J. Gower ◽  
Kerry Crone ◽  
Eben Alexander ◽  
David L. Kelly
Keyword(s):  
Candida Albicans ◽  
Blood Cells ◽  
White Blood Cells ◽  
Shunt Infection ◽  
Cerebrospinal Fluid Shunts ◽  
Previous Therapy ◽  
Relationship Of ◽  
The Relationship ◽  
Overall Mortality

Abstract Infection of cerebrospinal fluid shunts with Candida albicans is reported in two patients. Scanning electron microscopy in one case demonstrates the relationship of the Candida hyphae to the white blood cells and to silicone plastic. A review of 10 previously reported cases of Candida shunt infection indicates that the infection usually follows a major bacterial infection or direct contamination or occurs spontaneously, Previous therapy has usually involved removal of the shunt, and the role of parenteral antifungal therapy is still unclear. Overall mortality to date is 25%.

scholarly journals Rapid and sustained hematopoietic recovery in lethally irradiated mice transplanted with purified Thy-1.1lo Lin-Sca-1+ hematopoietic stem cells

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3758-3779 ◽  
Author(s):  
N Uchida ◽  
HL Aguila ◽  
WH Fleming ◽  
L Jerabek ◽  
IL Weissman
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Blood Cells ◽  
Critical Role ◽  
White Blood Cells ◽  
Cell Types ◽  
Dose Dependence ◽  
Hematopoietic Stem ◽  
Hematopoietic Recovery

Abstract Hematopoietic stem cells (HSCs) are believed to play a critical role in the sustained repopulation of all blood cells after bone marrow transplantation (BMT). However, understanding the role of HSCs versus other hematopoietic cells in the quantitative reconstitution of various blood cell types has awaited methods to isolate HSCs. A candidate population of mouse HSCs, Thy-1.1lo Lin-Sca-1+ cells, was isolated several years ago and, recently, this population has been shown to be the only population of BM cells that contains HSCs in C57BL/Ka-Thy-1.1 mice. As few as 100 of these cells can radioprotect 95% to 100% of irradiated mice, resulting long-term multilineage reconstitution. In this study, we examined the reconstitution potential of irradiated mice transplanted with purified Thy-1.1lo Lin-Sca-1+ BM cells. Donor-derived peripheral blood (PB) white blood cells were detected as early as day 9 or 10 when 100 to 1,000 Thy-1.1lo Lin-Sca-1+ cells were used, with minor dose-dependent differences. The reappearance of platelets by day 14 and thereafter was also seen at all HSC doses (100 to 1,000 cells), with a slight dose-dependence. All studied HSC doses also allowed RBC levels to recover, although at the 100 cell dose a delay in hematocrit recovery was observed at day 14. When irradiated mice were transplanted with 500 Thy-1.1lo Lin-Sca-1+ cells compared with 1 x 10(6) BM cells (the equivalent amount of cells that contain 500 Thy-1.1lo Lin-Sca-1+ cells as well as progenitor and mature cells), very little difference in the kinetics of recovery of PB, white blood cells, platelets, and hematocrit was observed. Surprisingly, even when 200 Thy1.1lo Lin-Sca- 1+ cells were mixed with 4 x 10(5) Sca-1- BM cells in a competitive repopulation assay, most of the early (days 11 and 14) PB myeloid cells were derived from the HSC genotype, indicating the superiority of the Thy-1.1lo Lin-Sca-1+ cells over Sca-1- cells even in the early phases of myeloid reconstitution. Within the Thy-1.1lo Lin-Sca-1+ population, the Rhodamine 123 (Rh123)hi subset dominates in PB myeloid reconstitution at 10 to 14 days, only to be overtaken by the Rh123lo subset at 3 weeks and thereafter. These findings indicate that HSCs can account for the early phase of hematopoietic recovery, as well as sustained hematopoiesis, and raise questions about the role of non-HSC BM populations in the setting of BMT.

scholarly journals Role of some members of chemokine/cytokine network in the pathogenesis of thalassemia and sickle cell hemoglobinopathies: a mini review

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Zahra Mousavi ◽  
Zinat Yazdani ◽  
Alireza Moradabadi ◽  
Fatemeh Hoseinpourkasgari ◽  
Gholamhossein Hassanshahi
Keyword(s):  
Endothelial Cells ◽  
Sickle Cell ◽  
Blood Cells ◽  
White Blood Cells ◽  
Cell Disease ◽  
Cytokine Network ◽  
Exact Role ◽  
Cytokines And Chemokines ◽  
Wide Range

Abstract The word of hemoglobinopathy is described for an array of disorders that affecting hemoglobin (Hb) functions. Hb is a molecule with 68 kDa molecular weight, serving as oxygen carrying metalloprotein. Hemoglobinopathy includes a wide range of Hb structural deficits varying from thalassemia to sickle cell disease. Cyto-chemokine network members are pivotally involved in the pathogenesis of hemoglobinopathies, however, the exact role of these mediators in the development of these disorders yet to be well addressed. Cytokines and chemokines are generated by inflamed endothelial cells that promote the expression of their respected receptors and further activate NF-κβ, recruit red blood cells (RBCs) and white blood cells (WBCs) toward the inflamed endothelium. Therefore, due to critical roles played by the cyto-chemokine network in several aspects of hemoglobinopathies pathophysiology including apoptosis of endothelial cells, RBC, WBC and etc.…, in the present review, we focused on the critical parts played by this network in the pathogenesis of hemoglobinopathies.

Hedgehog Signaling Regulates HSC Proliferation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1390-1390
Author(s):  
Akil Merchant ◽  
Giselle Joseph ◽  
William Matsui
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Blood Cells ◽  
White Blood Cells ◽  
Wild Type ◽  
Serial Blood ◽  
Myeloid Progenitor ◽  
Hh Signaling ◽  
Progenitor Compartment

Abstract Hedgehog (Hh) signaling is essential for normal development and is dysregulated in many cancers. Hh signaling is active in normal bone marrow and the majority of acute myeloid leukemias, however, the precise role of Hh signaling and its positive effector Gli1 in normal or malignant hematopoiesis is not known. We have analyzed the bone marrow of Gli1 null mice to understand the role of this transcription factor in normal hematopoiesis in order to gain insight into its potential role in leukemia. Gli1 null mice develop normally and have normal peripheral blood counts but the bone marrow shows skewing of the c-Kit+Sca1+Lin-neg (KSL) progenitor compartment with increased CD34negKSL long-term HSC (LT-HSC) and decreased 34+KSL short-term HSC (ST-HSC). An analogous difference was observed in the c-Kit+Sca1negLinneg (KL) myeloid progenitor compartment with an increase in FcRγlowCD34+KL common myeloid progenitors (CMP) and decrease in the FcRγhighCD34+KL granulocyte monocyte progenitors (GMP). We speculated that these differences could be due to impaired cell cycle since both the ST-HSC and GMP are more proliferative than LT-HSC and CMP, respectively. Cell cycle analysis by DNA content and BrdU pulse labeling (100mg/kg IP 14 hours prior to analysis) revealed a marked decrease of proliferation in the LT-HSC, ST-HSC, CMP, and GMP compartments of Gli1 null mice. We supported this conclusion by demonstrating that the bone marrow of Gli1 null mice are relatively radio-resistant. Mice exposed to 400 cGy of total body irradiation followed with serial blood counts revealed less severe nadir, but delayed rebound of white blood cells in Gli1 null mice. We further hypothesized that although Gli1 appears to be dispensable for steady-state peripheral hematopoiesis, it might be necessary for rapid proliferation of progenitors needed during stressed hematopoiesis. In brain development, where Hh signaling is much better understood, active Hh signaling is critical for regulating proliferation of neural stem cells and Gli1 activity significantly increases after depletion of neural progenitors with chemotherapy (Bai et al., Development, 2002). To extend this observation to hematopoiesis, we treated Gli1 null mice and wild-type litter-mates with 5-fluorouracil (5-FU) at 100mg/kg and measured serial blood counts. Gli1 null mice had a delayed recovery of total white blood cells and neutrophil counts at 6 days after 5-FU, but this difference normalized by 20 days after treatment. To confirm that this difference was due to impaired proliferation and not increased sensitivity to 5-FU, we treated Gli1 null and wild-type mice with G-CSF (10mcg/kg/day) for three days to stimulate neutrophil proliferation. Confirming our hypothesis, we observed an attenuated neutrophil response in G-CSF stimulated Gli1 null mice. In summary, we have demonstrated that Gli1 loss leads to decreased HSC and myeloid progenitor proliferation, which has important functional consequences for stress hematopoiesis. These data suggest that abnormal Hh activity in leukemia may be important for driving the uncontrolled proliferation of cancer cells. Gli1 null mice were a kind gift from Alexandra Joyner, Memorial Sloan-Kettering Cancer Center

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