scholarly journals Monocyte subset redistribution from blood to kidneys in patients with Puumala virus caused hemorrhagic fever with renal syndrome

2021 ◽  
Vol 17 (3) ◽  
pp. e1009400
Author(s):  
Sindhu Vangeti ◽  
Tomas Strandin ◽  
Sang Liu ◽  
Johanna Tauriainen ◽  
Anne Räisänen-Sokolowski ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Chemokine Receptors ◽  
Severe Disease ◽  
Hemorrhagic Fever ◽  
Puumala Virus ◽  
Monocyte Subset ◽  
Blood Monocytes ◽  
Peripheral Tissues ◽  
Hla Dr

Innate immune cells like monocytes patrol the vasculature and mucosal surfaces, recognize pathogens, rapidly redistribute to affected tissues and cause inflammation by secretion of cytokines. We previously showed that monocytes are reduced in blood but accumulate in the airways of patients with Puumala virus (PUUV) caused hemorrhagic fever with renal syndrome (HFRS). However, the dynamics of monocyte infiltration to the kidneys during HFRS, and its impact on disease severity are currently unknown. Here, we examined longitudinal peripheral blood samples and renal biopsies from HFRS patients and performed in vitro experiments to investigate the fate of monocytes during HFRS. During the early stages of HFRS, circulating CD14–CD16+ nonclassical monocytes (NCMs) that patrol the vasculature were reduced in most patients. Instead, CD14+CD16– classical (CMs) and CD14+CD16+ intermediate monocytes (IMs) were increased in blood, in particular in HFRS patients with more severe disease. Blood monocytes from patients with acute HFRS expressed higher levels of HLA-DR, the endothelial adhesion marker CD62L and the chemokine receptors CCR7 and CCR2, as compared to convalescence, suggesting monocyte activation and migration to peripheral tissues during acute HFRS. Supporting this hypothesis, increased numbers of HLA-DR+, CD14+, CD16+ and CD68+ cells were observed in the renal tissues of acute HFRS patients compared to controls. In vitro, blood CD16+ monocytes upregulated CD62L after direct exposure to PUUV whereas CD16– monocytes upregulated CCR7 after contact with PUUV-infected endothelial cells, suggesting differential mechanisms of activation and response between monocyte subsets. Together, our findings suggest that NCMs are reduced in blood, potentially via CD62L-mediated attachment to endothelial cells and monocytes are recruited to the kidneys during HFRS. Monocyte mobilization, activation and functional impairment together may influence the severity of disease in acute PUUV-HFRS.

Loss of CCR2 Expression and Functional Response to Monocyte Chemotactic Protein (MCP-1) During the Differentiation of Human Monocytes: Role of Secreted MCP-1 in the Regulation of the Chemotactic Response

Blood ◽  
1999 ◽  
Vol 94 (3) ◽  
pp. 875-883 ◽  
Author(s):  
Laura Fantuzzi ◽  
Paola Borghi ◽  
Veniero Ciolli ◽  
George Pavlakis ◽  
Filippo Belardelli ◽  
...  
Keyword(s):  
Chemokine Receptors ◽  
Human Peripheral Blood ◽  
Feedback Mechanism ◽  
Chemotactic Response ◽  
Receptor Expression ◽  
Blood Monocytes ◽  
Monocyte Chemotactic Protein ◽  
Ccr2 Expression ◽  
Chemotactic Protein

Human peripheral blood monocytes differentiate into macrophages when cultured in vitro for a few days. In the present study, we investigated the expression of C-C chemokine and CXCR4 receptors in monocytes at different stages of differentiation. Culturing of monocytes for 7 days resulted in a progressive decrease of the mRNA that encodes for CCR2 and CCR3, whereas the expression of mRNA for other chemokine receptors (CCR1, CCR4, CCR5, and CXCR4) was not substantially affected. The loss of CCR2 mRNA expression in 7-day–cultured macrophages was associated with a strong reduction in the receptor expression at the plasma membrane, as well as in the monocyte chemotactic protein (MCP-1) binding, as compared with freshly isolated monocytes. Furthermore, the biologic response to MCP-1, as measured by intracellular calcium ions increase and chemotactic response, was lost in 7-day–cultured macrophages. Differentiation of monocytes into macrophages also resulted in an increased secretion of MCP-1 that, at least in part, was responsible for the downmodulation of its receptor (CCR2). The loss of CCR2 expression and the parallel increase of MCP-1 secretion triggered by differentiation may represent a feedback mechanism in the regulation of the chemotactic response of monocytes/macrophages.

scholarly journals In-VitroDifferentiation of Mature Dendritic Cells From Human Blood Monocytes

1998 ◽  
Vol 6 (1-2) ◽  
pp. 25-39 ◽  
Author(s):  
Robert Gieseler ◽  
Dirk Heise ◽  
Afsaneh Soruri ◽  
Peter Schwartz ◽  
J. Hinrich Peters
Keyword(s):  
Dendritic Cells ◽  
Human Blood ◽  
T Cell Response ◽  
Blood Monocytes ◽  
Gm Csf ◽  
Hla Dr ◽  
Hla Dq ◽  
Specific Stimulation ◽  
Antigen Presenting

Representing the most potent antigen-presenting cells, dendritic cells (DC) can now be generated from human blood monocytes. We recently presented a novel protocol employing GM-CSF, IL-4, and IFN-γto differentiate monocyte-derived DCin vitro. Here, such cells are characterized in detail. Cells in culture exhibited both dendritic and veiled morphologies, the former being adherent and the latter suspended. Phenotypically, they were CD1a-/dim, CD11a+, CD11b++, CD11c+, CD14dim/-, CD16a-/dim, CD18+, CD32dim/-, CD33+, CD40+, CD45R0+, CD50+, CD54+, CD64-/dim, CD68+, CD71+, CD80dim, CD86+/++, MHC class I++/+++HLA-DR++/+++HLA-DP+, and HLA-DQ+. The DC stimulated a strong allogeneic T-cell response, and further evidence for their autologous antigen-specific stimulation is discussed. Although resembling a mature CD 11c+CD45R0+blood DC subset identified earlier, their differentiation in the presence of the Thl and Th2 cytokines IFN-γand IL-4 indicates that these DC may conform to mature mucosal DC.

scholarly journals Vascular endothelium as a regulator of granulopoiesis: production of colony-stimulating activity by cultured human endothelial cells

Blood ◽  
1980 ◽  
Vol 56 (6) ◽  
pp. 1060-1067
Author(s):  
PJ Quesenberry ◽  
MA Jr Gimbrone
Keyword(s):  
Endothelial Cells ◽  
Human Blood ◽  
Vascular Endothelium ◽  
Colony Formation ◽  
Primary Cultures ◽  
Blood Monocytes ◽  
Human Endothelial Cells ◽  
Colony Stimulating Activity ◽  
Marrow Cells

Colony-stimulating activity is a regulatory factor(s) that promotes differentiation of hemopoietic stem cells to mature granulocytes and macrophages; in man it has been found that blood monocytes, lymphocytes, and tissue macrophages produce it. In an effort to identify other potenitally physiologic tissue sources of colony- stimulating activity, we have studied the capacity of primary cultures of human vascular endothelial cells to produce colony-stimulating activity. Medium conditioned by incubation with endothelial cultures contained activity that promoted granulocyte-macrophage colony formation of nonadherent human and murine marrow cells. Exposure of endothelial cultures to 0.1–5.0 microgram/ml S. typhosa endotoxin for 6- 72 hr enhanced colony-stimulating activity production. Similarly, incubation of endothelial cells with lysates of human blood granulocytes, or cocultivation with intact granulocytes, resulted in increased colony-stimulating activity levels. In 7–14 day cultures, freshly isolated endothelial cells, incorporated into agar underlayers, consistently stimulated more colony formation by nonadherent human marrow cells than comparable numbers of blood monocytes. These data indicate that: (1) cultured human endothelial cells are a potent source of colony-stimulating activity; (2) they respond to endotoxin and granulocytes and their contents by producing increased amounts of CSA; and (3) they produce morea colony-stimulating activity, than human blood monocytes under standardized conditions in vitro. These observations suggest that the vascular endothelium may play a role in the physiologic regulation of granulopoiesis.

EFFECT OF MEASLES VACCINE ON MATURATION OF HUMAN DENDRITIC CELLS IN VITRO

2019 ◽  
pp. 61-66
Author(s):  
V.Yu. Talaev ◽  
O.N. Babaikina ◽  
M.V. Talaeva ◽  
E.V. Voronina ◽  
I.E. Zaichenko
Keyword(s):  
Dendritic Cells ◽  
Chemokine Receptors ◽  
Dendritic Cell Maturation ◽  
Measles Vaccine ◽  
Immature Dendritic Cells ◽  
Hla Dr ◽  
Important Means ◽  
Vaccine Prophylaxis ◽  
Human Dendritic Cells

The most important means of measles control is live measles vaccine, the high epidemiological effectiveness of which is confirmed by half a century of its use. There is a question of the need to further improve the effectiveness of vaccine prophylaxis, in particular, by increasing the immunogenicity of the used vaccine given the increase in the morbidity of measles in recent years. Investigation of effect features of existing vaccine variants is necessary to identify possible ways to increase their immunogenicity. We investigated the effect of measles culture live vaccine on the maturation of human dendritic cells – the most specialized antigen-presenting cells involved in the induction of an immune response. In vitro incubation of monocytic derived immature dendritic cells with the vaccine initiates the process of their partial maturation, which is manifested in an increase in the number of cells carrying molecules CD86, CD83 and ICOSL (CD275).At the same time they have a reduced expression level of the HLA-DR molecule and chemokine receptors CCR7 and CXCR5 involved in the migration of dendritic cells to peripheral lymphoid organs. In our opinion, the relative weak side of measles vaccine effect on dendritic cell maturation is a factor limiting the immunogenicity of the vaccine, which must be taken into account when developing new measles vaccines.

Immunogenecity of CML-DC Is Maintained upon Imatinib Mesylate: Implication for Vaccination Regimens.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4666-4666
Author(s):  
Theresia M. Westers ◽  
Jeroen J.W.M. Janssen ◽  
Niels C.L. Snoijs ◽  
Arjan A. van de Loosdrecht ◽  
Gert J. Ossenkoppele
Keyword(s):  
T Cell ◽  
Imatinib Mesylate ◽  
Chemokine Receptors ◽  
Residual Disease ◽  
Normal Subjects ◽  
Molecular Techniques ◽  
Imatinib Treatment ◽  
Dependent Manner ◽  
Hla Dr

Abstract Chronic myeloid leukemia (CML) is characterized by the presence of the Philidelphia chromosome which encodes for the fusion protein bcr-abl, a constitutively active tyrosine kinase. Imatinib mesylate (Gleevec, Novartis) is an inhibitor of the kinase activity of bcr-abl and therefore a treatment modality for CML. High rates of cytogenetic responses are found, although in many patients minimal residual disease (MRD) is detected by molecular techniques. Immunotherapy using leukemic dendritic cell (DC) based vaccination might be a feasible approach to eradicate MRD. In a pilot study on CML-DC-based vaccination in advanced CML DTH responses towards CML cells were achieved. (Ossenkoppele et al., Leukemia, 2003, 17, 1424). However, little is known about the effects of Imatinib mesylate on bcr-abl positive CML-DC during vaccination. In this study we investigated effects of Imatinib on culture of CML-DC, their viability, T cell stimulating and migratory capacity in vitro in 17 patients. Imatinib hardly affected the immunophenotypical profile of CML-DC. Expression of CD40, CD80, CD83, HLA-DR and chemokine receptors (CCR5, CCR7, CXCR4) remained stable during overnight exposure. Only the fluorescence intensity of CD86 was significantly higher (1–10μM, p=0.043) and that of CD54 significantly decreased in the highest Imatinib concentration tested (p=0.043). Exposure of Imatinib-free cultured CML-DC to Imatinib significantly reduced the recovery of viable cells and hence the DC yield in a dose-dependent manner (5.3–26% reduction after 20h. for 1–10μM, p=0.043). Migration of mature CML-DC towards CCL19 (MIP3β) was significantly improved in the presence of 1 and 5μM Imatinib which implies increased ability to reach the lymph nodes (p=0.043, mean 27, 36 and 34% migration for 0, 1 and 5μM Imatinib, respectively). Imatinib did not affect T cell stimulating capacity of CML-DC, except at concentrations higher than 3μM (p=0.028). No significant changes were observed for Imatinib exposure of CD34+ DC isolated from normal subjects. In conclusion, Imatinib at low concentrations maintains the immunogenecity of CML-DC. Since Imatinib plasma levels in CML patients are 1.5 and 3.0μM upon 400 and 800mg daily, respectively, our data justify continuation of Imatinib treatment during CML-DC-based vaccination regimens.

TRAF-1 Deficient Mice Show Impaired Monocyte Recruitment and Decreased Atherogenesis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 696-696
Author(s):  
Anna Missiou ◽  
Natascha Köstlin ◽  
Christian Münkel ◽  
Dietmar Pfeifer ◽  
Katja Zirlik ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Chemokine Receptors ◽  
Inflammatory Diseases ◽  
Inflammatory Cells ◽  
Adaptor Proteins ◽  
High Cholesterol Diet ◽  
Cell Content ◽  
Monocyte Recruitment

Abstract Members of the tumor necrosis factor (TNF) interleukin/toll-like receptor superfamily such as CD40L, TNFa, and IL-1b potently promote atherogenesis in mice and likely also in humans. TNF receptor associated factors (TRAFs) are cytoplasmic adaptor proteins for this group of cytokines. We recently reported over-expression of TRAFs in murine and human atheromata and demonstrated dependency of classic inflammatory functions on TRAFs in endothelial cells and macrophages. Here we test the hypothesis that TRAF-1 modulates atherogenesis in vivo. TRAF-1--/LDLR--mice fed a high cholesterol diet for 18 weeks developed significantly smaller atherosclerotic lesions compared with LDLR--controls. Intimal lesion size decreased by up to 56±6% and 33±5% in sections of the aortic arch and aortic root, respectively (n>10 per group, P<0.01 each). Plaques of TRAF-1-deficient animals contained up to 46±9% and 55±4% fewer macrophages while smooth muscle cell content increased by up to 32±6 and 36±7%, characteristics associated with non disrupted plaques in humans. Lipid content, collagen content, and lymphocyte content remained unchanged. In vitro, gene expression profiling revealed reduced expression of adhesion molecules (VCAM-1, ICAM-1), chemokines (CCL2, CXCL2), and growth factors (M-CSF) in TRAF-1-deficient endothelial cells as well as of integrins (CD29, CD11b) and chemokines/chemokine receptors (CXCL2, CCR1) in TRAF-1-deficient macrophages, verified by siRNA studies in human cells. Finally, both deficiency of TRAF-1 in endothelial cells and neutrophils/monocytes reduced adhesion of inflammatory cells to the endothelium in static and dynamic adhesion assays. We present the novel finding that TRAF 1 deficiency attenuates atherogenesis in mice, an effect most likely mediated by impaired monocyte recruitment to the vessel wall. These data identify TRAF-1 as potential treatment target for chronic inflammatory diseases such as atherosclerosis.

scholarly journals High-Dose Methylprednisolone Reduces Cytokine-Induced Adhesion Molecules on Human Brain Endothelium

2000 ◽  
Vol 27 (3) ◽  
pp. 241-244 ◽  
Author(s):  
Maurizio Gelati ◽  
Elena Corsini ◽  
Anna Dufour ◽  
Giorgio Massa ◽  
Sergio Giombini ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Human Brain ◽  
Adhesion Molecules ◽  
High Dose ◽  
Dependent Manner ◽  
Brain Endothelium ◽  
Hla Dr ◽  
High Dose Methylprednisolone ◽  
Brain Microvessel

Objective:We investigated the in vitro effects of low- and high-dose methylprednisolone (MP) on the cytokine-induced expression of HLA-DR, ICAM-1 and VCAM-1 on human brain microvessel endothelial cells (HBMECs).Methods:Brain endothelium was obtained from microvessels included in the apparently normal white matter of surgical specimens of nine patients. Cells were stained with monoclonal antibodies anti-HLA-DR, anti-ICAM-1 and anti-VCAM-1 and analysed by flow cytometry as fluorescence histograms. The mean fluorescence intensity (MFI) of HBMECs treated with different stimuli was calculated.Results:3-IFN-induced HLA-DR was down-regulated in a dose-dependent manner by MP. High-dose MP reduced the TNF-3-induced ICAM-1 and VCAM-1 expression.Conclusion:The down-regulation of adhesion molecules on cerebral endothelial cells could decrease mononuclear cell transmigration through the blood brain barrier and consequently the perivascular infiltrates. The results add support to the rationale for high-dose MP treatment in multiple sclerosis relapses.

scholarly journals Fractalkine Preferentially Mediates Arrest and Migration of CD16+ Monocytes

2003 ◽  
Vol 197 (12) ◽  
pp. 1701-1707 ◽  
Author(s):  
Petronela Ancuta ◽  
Ravi Rao ◽  
Ashlee Moses ◽  
Andrew Mehle ◽  
Sunil K. Shaw ◽  
...  
Keyword(s):  
Chemokine Receptors ◽  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Monocyte Subset ◽  
Blood Monocytes ◽  
Monocyte Chemoattractant Protein 1 ◽  
Pathological Conditions ◽  
Normal Individuals ◽  
And Migration

CD16+ monocytes represent 5–10% of peripheral blood monocytes in normal individuals and are dramatically expanded in several pathological conditions including sepsis, human immunodeficiency virus 1 infection, and cancer. CD16+ monocytes produce high levels of proinflammatory cytokines and may represent dendritic cell precursors in vivo. The mechanisms that mediate the recruitment of CD16+ monocytes into tissues remain unknown. Here we investigate molecular mechanisms of CD16+ monocyte trafficking and show that migration of CD16+ and CD16− monocytes is mediated by distinct combinations of adhesion molecules and chemokine receptors. In contrast to CD16− monocytes, CD16+ monocytes expressed high CX3CR1 and CXCR4 but low CCR2 and CD62L levels and underwent efficient transendo-thelial migration in response to fractalkine (FKN; FKN/CX3CL1) and stromal-derived factor 1α (CXCL12) but not monocyte chemoattractant protein 1 (CCL2). CD16+ monocytes arrested on cell surface–expressed FKN under flow with higher frequency compared with CD16− monocytes. These results demonstrate that FKN preferentially mediates arrest and migration of CD16+ monocytes and suggest that recruitment of this proinflammatory monocyte subset to vessel walls via the CX3CR1-FKN pathway may contribute to vascular and tissue injury during pathological conditions.

Involvement of functional autoantibodies against vascular receptors in systemic sclerosis

2010 ◽  
Vol 70 (3) ◽  
pp. 530-536 ◽  
Author(s):  
Gabriela Riemekasten ◽  
Aurélie Philippe ◽  
Melanie Näther ◽  
Torsten Slowinski ◽  
Dominik N Müller ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Systemic Sclerosis ◽  
Transforming Growth Factor ◽  
Solid Phase ◽  
Biological Effects ◽  
Severe Disease ◽  
Study Cohort ◽  
Serum Samples ◽  
Related Mortality

BackgroundSystemic sclerosis (SSc) features autoimmunity, vasculopathy and tissue fibrosis. The renin-angiotensin and endothelin systems have been implicated in vasculopathy and fibrosis. A role for autoantibody-mediated receptor stimulation is hypothesised, linking three major pathophysiological features consistent with SSc.MethodsSerum samples from 478 patients with SSc (298 in the study cohort and 180 from two further independent cohorts), 372 healthy subjects and 311 control-disease subjects were tested for antibodies against angiotensin II type 1 receptor (AT1R) and endothelin-1 type A receptor (ETAR) by solid phase assay. Binding specificities were tested by immunoprecipitation. The biological effects of autoantibodies in microvascular endothelial cells in vitro were also determined, as well as the quantitative differences in autoantibody levels on specific organ involvements and their predictive value for SSc-related mortality.ResultsAnti-AT1R and anti-ETAR autoantibodies were detected in most patients with SSc. Autoantibodies specifically bound to respective receptors on endothelial cells. Higher levels of both autoantibodies were associated with more severe disease manifestations and predicted SSc-related mortality. Both autoantibodies exert biological effects as they induced extracellular signal-regulated kinase 1/2 phosphorylation and increased transforming growth factor β gene expression in endothelial cells which could be blocked with specific receptor antagonists.ConclusionsFunctional autoimmunity directed at AT1R and ETAR is common in patients with SSc. AT1R and ETAR autoantibodies could contribute to disease pathogenesis and may serve as biomarkers for risk assessment of disease progression.

scholarly journals Immunogenic Properties of MVs Containing Structural Hantaviral Proteins: An Original Study

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 93
Author(s):  
Layaly Shkair ◽  
Ekaterina Evgenevna Garanina ◽  
Ekaterina Vladimirovna Martynova ◽  
Alena Igorevna Kolesnikova ◽  
Svetlana Sergeevna Arkhipova ◽  
...  
Keyword(s):  
Hemorrhagic Fever ◽  
Original Study ◽  
Puumala Virus ◽  
Global Public Health ◽  
Public Health Threat ◽  
Delivery Vehicles ◽  
Cellular Immune ◽  
Immunogenic Properties

Hemorrhagic fever with renal syndrome (HFRS) is an emerging infectious disease that remains a global public health threat. The highest incidence rate is among zoonotic disease cases in Russia. Most cases of HFRS are reported in the Volga region of Russia, which commonly identifies the Puumala virus (PUUV) as a pathogen. HFRS management is especially challenging due to the lack of specific treatments and vaccines. This study aims to develop new approaches for HFRS prevention. Our goal is to test the efficacy of microvesicles (MVs) as PUUV nucleocapsid (N) and glycoproteins (Gn/Gc) delivery vehicles. Our findings show that MVs could deliver the PUUV N and Gn/Gc proteins in vitro. We have also demonstrated that MVs loaded with PUUV proteins could elicit a specific humoral and cellular immune response in vivo. These data suggest that an MV-based vaccine could control HFRS.

Sign in / Sign up

Export Citation Format

Share Document