Alendronate Stimulates Expression of Functional Surface Molecules ICAM-1, HLA-DR, and B7-2 on Human Monocytes

Although known as a Na,K-ATPase inhibitor, several other cellular and systemic actions have been ascribed to the steroid Ouabain (Oua). Particularly in the immune system, our group showed that Ouabain acts on decreasing lymphocyte proliferation, synergizing with glucocorticoids in spontaneous thymocyte apoptosis, and also lessening CD14 expression and blocking CD16 upregulation on human monocytes. However, Ouabain effects on dendritic cells (DCs) were not explored so far. Considering the peculiar plasticity and the importance of DCs in immune responses, the aim of our study was to investigate DC maturation under Ouabain influence. To generate immature DCs, human monocytes were cultured with IL-4 and GM-CSF (5 days). To investigate Ouabain role on DC activation, DCs were stimulated with TNF-αfor 48 h in the presence or absence of Ouabain. TNF-induced CD83 expression and IL-12 production were abolished in DCs incubated with 100 nM Ouabain, though DC functional capacity concerning lymphocyte activation remained unaltered. Nevertheless, TNF-α-induced antigen capture downregulation, another maturation marker, occurred even in the presence of Ouabain. Besides, Ouabain increased HLA-DR and CD86 expression, whereas CD80 expression was maintained. Collectively, our results suggest that DCs respond to Ouabain maturating into a distinct category, possibly contributing to the balance between immunity and tolerance.

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Granulocyte-macrophage colony stimulating factor stimulates both HLA-DR expression and cytokine production by human monocytes

Cytokine ◽

10.1016/1043-4666(89)91221-0 ◽

1989 ◽

Vol 1 (1) ◽

pp. 101

Keyword(s):

Cytokine Production ◽

Human Monocytes ◽

Colony Stimulating Factor ◽

Hla Dr ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

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Decrease of HLA-DR antigen expression by human monocytes during cultivation in absence of exogenous or endogenous interferon-γ

Immunology Letters ◽

10.1016/0165-2478(85)90184-1 ◽

1985 ◽

Vol 10 (2) ◽

pp. 103-107 ◽

Cited By ~ 5

Author(s):

H.-D. Volk ◽

S.R. Waschke ◽

W. Diezel ◽

R. Grunow ◽

R.v. Baehr ◽

...

Keyword(s):

Antigen Expression ◽

Interferon Γ ◽

Human Monocytes ◽

Hla Dr

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Fibronectin receptors of phagocytes. Characterization of the Arg-Gly-Asp binding proteins of human monocytes and polymorphonuclear leukocytes.

Journal of Experimental Medicine ◽

10.1084/jem.167.3.777 ◽

1988 ◽

Vol 167 (3) ◽

pp. 777-793 ◽

Cited By ~ 99

Author(s):

E J Brown ◽

J L Goodwin

Keyword(s):

Surface Molecule ◽

Human Monocytes ◽

Ligand Specificity ◽

Cell Binding ◽

Antigenic Analysis ◽

Vitronectin Receptor ◽

Surface Molecules ◽

Rgd Sequence ◽

Single Receptor

We have defined the cell surface molecules of human monocytes and PMN that bind to the chymotryptic cell binding domain of Fn and to a synthetic peptide, KYAVTGRGDS, based on the sequence of Fn, by affinity chromatography. Monocytes express two receptors that differ in their affinity for CBD-Sepharose and peptide-Sepharose, but that both recognize the RGD sequence. Only a single receptor is purified from PMN, which resembles the monocyte surface molecule that binds to peptide-Sepharose. These receptors are not part of the Mac-1, LFA-1, p(150,95) family, but do have homology to the platelet Fn receptor, gpIIb/IIIa. Interestingly, the antigenic crossreactivity between gpIIb/IIIa and the phagocyte receptors purified on peptide-Sepharose is largely in the beta chain of the receptors. The alpha chains appear to be distinct, based on molecular weight, antigenic analysis, and ligand specificity. This receptor also seems to be the surface molecule on monocytes that is critical for phagocytosis enhancement by Fn. Thus, we have defined the phagocyte Fn receptor that transduces the signal for increased phagocytosis by monocytes; it may be a third member of a family of adhesion molecules that includes the gpIIb/IIIa of platelets and the vitronectin receptor of fibroblasts.

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SARS-CoV-2 induces inflammasome-dependent pyroptosis and downmodulation of HLA-DR in human monocytes

10.1101/2020.08.25.20182055 ◽

2020 ◽

Author(s):

André C. Ferreira ◽

Vinicius Cardoso Soares ◽

Isaclaudia G. de Azevedo-Quintanilha ◽

Suelen da Silva Gomes Dias ◽

Natalia Fintelman-Rodrigues ◽

...

Keyword(s):

Immune Response ◽

Cell Death ◽

Severe Acute Respiratory Syndrome ◽

Inflammatory Response ◽

Inflammatory Cell ◽

Viral Infections ◽

Relevant Information ◽

Inflammasome Activation ◽

Human Monocytes ◽

Hla Dr

AbstractInfection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with leukopenia and uncontrolled inflammatory response in critically ill patients. A better comprehension of SARS-CoV-2-induced monocyte death is essential for the identification of therapies capable to control the hyper-inflammation and reduce viral replication in patients with COVID-19. Here, we show that SARS-CoV-2 induces inflammasome activation and cell death by pyroptosis in human monocytes, experimentally infected and from patients under intensive care. Pyroptosis was dependent on caspase-1 engagement, prior to IL-1ß production and inflammatory cell death. Monocytes exposed to SARS-CoV-2 downregulate HLA-DR, suggesting a potential limitation to orchestrate the immune response. Our results originally describe mechanisms by which monocytes, a central cellular component recruited from peripheral blood to respiratory tract, succumb to control severe 2019 coronavirus disease (COVID-19).Author summarySince its emergence in China in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused thousands of deaths worldwide. Currently, the number of individuals infected with SARS-CoV-2 and in need of antiviral, anti-inflammatory, anticoagulant and more invasive treatments has overwhelmed the health systems worldwide. In our study, we found that SARS-CoV-2 is capable of inducing inflammatory cell death in human monocytes, one of the main cell types responsible for anti-SARS-CoV-2 immune response. As a consequence of this intracellular inflammatory mechanism (inflammasome engagement), an exacerbated production of inflammatory mediators occurs. The infection also decreases the expression of HLA-DR in monocytes, a molecule related to the orchestration of the immune response in case of viral infections. We also demonstrated that the HIV-1 protease inhibitor, atazanavir (ATV), prevented the uncontrolled inflammatory response, cell death and reduction in HLA-DR expression in SARS-CoV-2-infected monocytes. Our study provides relevant information on the effects of SARS-CoV-2 infection on human monocytes, as well as on the effect of ATV in preventing these pathological effects on the host.

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Endogenous NGF regulates CGRP expression in human monocytes, and affects HLA-DR and CD86 expression and IL-10 production

Blood ◽

10.1182/blood-2004-10-4055 ◽

2005 ◽

Vol 106 (10) ◽

pp. 3507-3514 ◽

Cited By ~ 56

Author(s):

Luisa Bracci-Laudiero ◽

Luigi Aloe ◽

Maria Cristina Caroleo ◽

Pasquale Buanne ◽

Nicola Costa ◽

...

Keyword(s):

Mhc Class Ii ◽

T Cell Activation ◽

Cell Activation ◽

Human Leukocyte ◽

Interleukin 10 ◽

Human Monocytes ◽

Leukocyte Antigen ◽

Physiologic Mechanism ◽

Hla Dr ◽

Antigen Presenting

AbstractOur recent results on autocrine nerve growth factor (NGF) synthesis in B lymphocytes, which directly regulates the expression and release of calcitonin gene-related peptide (CGRP), a neuropeptide known to down-regulate immune response, led us to propose an anti-inflammatory action of NGF. In the present work, we investigated whether the endogenous synthesis of NGF can regulate the expression of CGRP in other antigen-presenting cells, such as monocytes, and whether this may have a functional effect. Our data indicate that human monocytes synthesize basal levels of NGF and CGRP and that, following lipopolysaccharide (LPS) stimulation, NGF and CGRP expression are both up-regulated. When endogenous NGF is neutralized, the up-regulation of CGRP expression induced by LPS is inhibited. The expression of membrane molecules involved in T-cell activation such as human leukocyte antigen-DR (HLA-DR) and CD86 is affected by endogenous NGF, and similar effects were obtained using a CGRP1 receptor antagonist. In addition, NGF deprivation in LPS-treated monocytes significantly decreases interleukin 10 (IL-10) synthesis. Our findings indicate that endogenous NGF synthesis has a functional role and may represent a physiologic mechanism to down-regulate major histocompatibility complex (MHC) class II and CD86 expression and alter the development of immune responses.

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