scholarly journals Galectin-3 Activates the NADPH-Oxidase in Exudated but not Peripheral Blood Neutrophils

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3430-3438 ◽  
Author(s):  
Anna Karlsson ◽  
Per Follin ◽  
Hakon Leffler ◽  
Claes Dahlgren
Keyword(s):  
Nadph Oxidase ◽  
Peripheral Blood ◽  
Oxidative Response ◽  
Galectin 3 ◽  
Blood Neutrophils ◽  
Intracellular Organelles ◽  
Neutrophil Response ◽  
Neutrophil Respiratory Burst

Abstract Galectin-3, a lactose-binding mammalian lectin that is secreted from activated macrophages, basophils, and mast cells, was investigated with respect to its ability to activate the human neutrophil NADPH-oxidase. The galectin-3–induced activity was determined with in vivo exudated cells (obtained from a skin chamber) and compared with that of peripheral blood neutrophils. Galectin-3 was found to be a potent activator of the NADPH-oxidase only in exudated neutrophils and the binding of galectin-3 to the surface of these cells was increased compared with peripheral blood cells. Different in vitro priming protocols resulting in degranulation were used to mimic the exudation process in terms of increasing the receptor exposure on the cell surface. Galectin-3 could induce an oxidative response similar to that in exudated cells only after a significant amount of the intracellular organelles had been mobilized. This increase in oxidative response was paralleled by an increased binding of galectin-3 to the surface of the cells. The major conclusion of the study is that galectin-3 is a potent stimulus of the neutrophil respiratory burst, provided that the cells have first experienced an extravasation process. The results also imply that the neutrophil response to galectin-3 could be mediated through receptors mobilized from intracellular granules, and we report the presence of galectin-3–binding proteins in such organelles.

scholarly journals Galectin-3 Activates the NADPH-Oxidase in Exudated but not Peripheral Blood Neutrophils

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3430-3438 ◽  
Author(s):  
Anna Karlsson ◽  
Per Follin ◽  
Hakon Leffler ◽  
Claes Dahlgren
Keyword(s):  
Nadph Oxidase ◽  
Peripheral Blood ◽  
Oxidative Response ◽  
Galectin 3 ◽  
Blood Neutrophils ◽  
Intracellular Organelles ◽  
Neutrophil Response ◽  
Neutrophil Respiratory Burst

Galectin-3, a lactose-binding mammalian lectin that is secreted from activated macrophages, basophils, and mast cells, was investigated with respect to its ability to activate the human neutrophil NADPH-oxidase. The galectin-3–induced activity was determined with in vivo exudated cells (obtained from a skin chamber) and compared with that of peripheral blood neutrophils. Galectin-3 was found to be a potent activator of the NADPH-oxidase only in exudated neutrophils and the binding of galectin-3 to the surface of these cells was increased compared with peripheral blood cells. Different in vitro priming protocols resulting in degranulation were used to mimic the exudation process in terms of increasing the receptor exposure on the cell surface. Galectin-3 could induce an oxidative response similar to that in exudated cells only after a significant amount of the intracellular organelles had been mobilized. This increase in oxidative response was paralleled by an increased binding of galectin-3 to the surface of the cells. The major conclusion of the study is that galectin-3 is a potent stimulus of the neutrophil respiratory burst, provided that the cells have first experienced an extravasation process. The results also imply that the neutrophil response to galectin-3 could be mediated through receptors mobilized from intracellular granules, and we report the presence of galectin-3–binding proteins in such organelles.

scholarly journals Wheat Germ Agglutinin Induces NADPH-Oxidase Activity in Human Neutrophils by Interaction with Mobilizable Receptors

1999 ◽  
Vol 67 (7) ◽  
pp. 3461-3468 ◽  
Author(s):  
Anna Karlsson
Keyword(s):  
Sialic Acid ◽  
Nadph Oxidase ◽  
Peripheral Blood ◽  
Wheat Germ Agglutinin ◽  
Wheat Germ ◽  
Human Neutrophils ◽  
Extracellular Milieu ◽  
Blood Neutrophils

ABSTRACT Wheat germ agglutinin (WGA), a lectin with specificity forN-acetylglucosamine and sialic acid, was investigated with respect to its ability to activate the NADPH-oxidase of in vivo-exudated neutrophils (obtained from a skin chamber), and the activity was compared to that of peripheral blood neutrophils. The exudate cells responded to WGA, by both releasing reactive oxygen species into the extracellular milieu and producing oxygen metabolites intracellularly. The peripheral blood cells were unresponsive. To mimic the in vivo-exuded neutrophils with regards to receptor exposure, peripheral blood neutrophils were induced to mobilize their granules and vesicles to varying degrees (in vitro priming), prior to challenge with WGA. The oxidative response to WGA increased with increasing levels of granule mobilization, and the receptor(s) could be shown to reside in the secretory vesicles and/or the gelatinase granules in resting neutrophils. Several WGA-binding glycoproteins were detected in subcellular fractions containing these organelles. The extra- and intracellular NADPH-oxidase responses showed differences in sialic acid dependency, indicating that these two responses are mediated by different receptor structures.

scholarly journals NFIL3 Facilitates Neutrophil Autophagy, Neutrophil Extracellular Trap Formation and Inflammation During Gout via REDD1-Dependent mTOR Inactivation

2021 ◽  
Vol 8 ◽  
Author(s):  
Honghu Tang ◽  
Chunyu Tan ◽  
Xue Cao ◽  
Yi Liu ◽  
Hua Zhao ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Expression Patterns ◽  
Gouty Arthritis ◽  
Mtor Pathway ◽  
Neutrophil Extracellular Trap ◽  
Inflammatory Factors ◽  
Loss Of Function ◽  
Blood Neutrophils

Autophagy pathways play an important role in immunity and inflammation via pathogen clearance mechanisms mediated by immune cells, such as macrophages and neutrophils. In particular, autophagic activity is essential for the release of neutrophil extracellular traps (NETs), a distinct form of active neutrophil death. The current study set out to elucidate the mechanism of the NFIL3/REDD1/mTOR axis in neutrophil autophagy and NET formation during gout inflammation. Firstly, NFIL3 expression patterns were determined in the peripheral blood neutrophils of gout patients and monosodium urate (MSU)-treated neutrophils. Interactions between NFIL3 and REDD1 were identified. In addition, gain- or loss-of-function approaches were used to manipulate NFIL3 and REDD1 in both MSU-induced neutrophils and mice. The mechanism of NFIL3 in inflammation during gout was evaluated both in vivo and in vitro via measurement of cell autophagy, NET formation, MPO activity as well as levels of inflammatory factors. NFIL3 was highly-expressed in both peripheral blood neutrophils from gout patients and MSU-treated neutrophils. NFIL3 promoted the transcription of REDD1 by binding to its promoter. REDD1 augmented neutrophil autophagy and NET formation by inhibiting the mTOR pathway. In vivo experimental results further confirmed that silencing of NFIL3 reduced the inflammatory injury of acute gouty arthritis mice by inhibiting the neutrophil autophagy and NET formation, which was associated with down-regulation of REDD1 and activation of the mTOR pathway. Taken together, NFIL3 can aggravate the inflammatory reaction of gout by stimulating neutrophil autophagy and NET formation via REDD1/mTOR, highlighting NFIL3 as a potential therapeutic target for gout.

Downregulation of blood and bone marrow neutrophils decreases expression of acute lung injury in sheep

1992 ◽  
Vol 263 (5) ◽  
pp. H1492-H1498
Author(s):  
P. J. McKenna ◽  
D. L. Rosolia ◽  
Y. Ishihara ◽  
K. H. Albertine ◽  
N. C. Staub ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Peripheral Blood ◽  
Pulmonary Circulation ◽  
Tissue Injury ◽  
Blood Neutrophils ◽  
Superoxide Release

We have shown that infusion of zymosan-activated plasma (ZAP) in sheep causes acute lung injury and downregulates peripheral blood neutrophils in that elicited superoxide release is reduced for at least 24 h after the infusion. The present study was designed to test the following hypotheses: 1) peripheral blood neutrophils are representative of neutrophils marginated in the pulmonary circulation, 2) blood neutrophils are downregulated because neutrophils developing in bone marrow are similarly affected, and 3) downregulated neutrophils have a reduced capacity to produce tissue injury. In a series of experiments in 21 sheep, we showed that elicited superoxide release was similar in peripheral blood neutrophils and in marginated neutrophils washed out of the pulmonary vascular bed. Measurements of superoxide release from blood and bone marrow neutrophils collected 2-24 h after ZAP infusion revealed progressive downregulation with time and greater downregulation of superoxide release in bone marrow neutrophils compared with peripheral blood neutrophils. Finally, after downregulating peripheral blood neutrophils, subsequent infusion of ZAP in conscious sheep produced sequestration of neutrophils in the pulmonary circulation but failed to produce a sustained increase in lung lymph protein clearance. The results suggest that neutrophil downregulation, as measured in vitro, is expressed in vivo as reduced ability of neutrophils to produce tissue injury when challenged by an activating agent.

Downmodulation of IL-8 receptors, type A and type B, on human lung neutrophils in vivo

1997 ◽  
Vol 273 (3) ◽  
pp. L618-L625 ◽  
Author(s):  
K. Soejima ◽  
S. Fujishima ◽  
H. Nakamura ◽  
Y. Waki ◽  
M. Nakamura ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Type A ◽  
Type B ◽  
Low Level ◽  
Blood Neutrophils ◽  
Vitro Analysis ◽  
High Level ◽  
In Vitro Analysis

We examined the expression of interleukin (IL)-8 receptors (Rs), type A (IL-8-RA) and type B (IL-8-RB), on peripheral blood and bronchoalveolar lavage (BAL) fluid neutrophils; we also examined IL-8 and other chemoattractants in the epithelial lining fluid (ELF) of patients with chronic lower respiratory tract infection (CLI) to elucidate the in vivo regulation of IL-8Rs. Neutrophils were stained with monoclonal antibodies specific for IL-8-RA and IL-8-RB. We detected higher levels of IL-8 (81.6 +/- 25.4 ng/ml, mean +/- SE), leukotriene (LT) B4, and IL-1 beta in the ELF of the CLI patients than in their serum (P < 0.05). The expression of IL-8Rs on BAL neutrophils was significantly lower than that on peripheral blood neutrophils (P < 0.01 for both). In vitro analysis showed that low-level IL-8 (50 ng/ml) alone did not affect IL-8R expression but that it was downregulated by high-level IL-8 (500 ng/ml) alone and by low-level IL-8 in combination with LTB4 or IL-1 beta. Staurosporine reduced the downmodulation by low-level IL-8 plus LTB4 or IL-1 beta but not by high-level IL-8 alone. We speculate that pulmonary IL-8-RA and IL-8-RB may have been downmodulated by the combined effect of local chemoattractants through, in part, a protein kinase C-dependent mechanism.

scholarly journals Cytokine-Activated Endothelial Cells Delay Neutrophil Apoptosis in Vitro and in Vivo

1999 ◽  
Vol 190 (7) ◽  
pp. 923-934 ◽  
Author(s):  
Angela Coxon ◽  
Tao Tang ◽  
Tanya N. Mayadas
Keyword(s):  
Endothelial Cells ◽  
Peripheral Blood ◽  
Neutrophil Apoptosis ◽  
Wild Type ◽  
Gm Csf ◽  
Acute Meningitis ◽  
Blood Neutrophils ◽  
And Function

The activation of endothelium is important in recruiting neutrophils to sites of inflammation and in modulating their function. We demonstrate that conditioned medium from cultured, activated endothelial cells acts to significantly delay the constitutive apoptosis of neutrophils, resulting in their enhanced survival and increased phagocytic function. The antiapoptotic activity is, in part, attributable to granulocyte/macrophage colony-stimulating factor (GM-CSF) secreted by activated endothelial cells. The in vivo relevance of these findings was investigated in a cytokine-induced model of acute meningitis in mice. Peripheral blood neutrophils (PBNs) from mice with meningitis exhibited a delay in apoptosis compared with untreated mice. Furthermore, neutrophils recovered from the inflamed cerebrospinal fluid (CSF) exhibited enhanced survival compared with neutrophils isolated from the peripheral blood of the same animals. In unchallenged GM-CSF–deficient mice, the apoptosis of circulating PBNs was similar to wild-type animals; however, after cytokine-induced meningitis, the delay in neutrophil apoptosis typically observed in wild-type mice was attenuated. In contrast, the apoptosis of neutrophils recovered from the CSF of mice of both genotypes was comparable. Taken together, these studies suggest that neutrophil apoptosis is regulated during an inflammatory response, in both intravascular and extravascular compartments. GM-CSF released by activated endothelium can act to increase neutrophil survival and function in the peripheral blood, whereas other factor(s) appear to perform this function in the extravascular space.

scholarly journals Functional and Transcriptional Adaptations of Blood Monocytes Recruited to the Cystic Fibrosis Airway Microenvironment In Vitro

2021 ◽  
Vol 22 (5) ◽  
pp. 2530
Author(s):  
Bijean D. Ford ◽  
Diego Moncada Giraldo ◽  
Camilla Margaroli ◽  
Vincent D. Giacalone ◽  
Milton R. Brown ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Bactericidal Activity ◽  
Scavenger Receptor ◽  
Receptor Expression ◽  
Blood Monocytes ◽  
Bacterial Killing ◽  
Blood Neutrophils ◽  
Vitro Model

Cystic fibrosis (CF) lung disease is dominated by the recruitment of myeloid cells (neutrophils and monocytes) from the blood which fail to clear the lung of colonizing microbes. In prior in vitro studies, we showed that blood neutrophils migrated through the well-differentiated lung epithelium into the CF airway fluid supernatant (ASN) mimic the dysfunction of CF airway neutrophils in vivo, including decreased bactericidal activity despite an increased metabolism. Here, we hypothesized that, in a similar manner to neutrophils, blood monocytes undergo significant adaptations upon recruitment to CFASN. To test this hypothesis, primary human blood monocytes were transmigrated in our in vitro model into the ASN from healthy control (HC) or CF subjects to mimic in vivo recruitment to normal or CF airways, respectively. Surface phenotype, metabolic and bacterial killing activities, and transcriptomic profile by RNA sequencing were quantified post-transmigration. Unlike neutrophils, monocytes were not metabolically activated, nor did they show broad differences in activation and scavenger receptor expression upon recruitment to the CFASN compared to HCASN. However, monocytes recruited to CFASN showed decreased bactericidal activity. RNASeq analysis showed strong effects of transmigration on monocyte RNA profile, with differences between CFASN and HCASN conditions, notably in immune signaling, including lower expression in the former of the antimicrobial factor ISG15, defensin-like chemokine CXCL11, and nitric oxide-producing enzyme NOS3. While monocytes undergo qualitatively different adaptations from those seen in neutrophils upon recruitment to the CF airway microenvironment, their bactericidal activity is also dysregulated, which could explain why they also fail to protect CF airways from infection.

scholarly journals Macropinocytosis requires Gal-3 in a subset of patient-derived glioblastoma stem cells

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Laetitia Seguin ◽  
Soline Odouard ◽  
Francesca Corlazzoli ◽  
Sarah Al Haddad ◽  
Laurine Moindrot ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Survival ◽  
Small Gtpases ◽  
Molecular Signature ◽  
Carbohydrate Binding ◽  
Pancreatic Cancers ◽  
Galectin 3 ◽  
Pharmacologic Inhibition

AbstractRecently, we involved the carbohydrate-binding protein Galectin-3 (Gal-3) as a druggable target for KRAS-mutant-addicted lung and pancreatic cancers. Here, using glioblastoma patient-derived stem cells (GSCs), we identify and characterize a subset of Gal-3high glioblastoma (GBM) tumors mainly within the mesenchymal subtype that are addicted to Gal-3-mediated macropinocytosis. Using both genetic and pharmacologic inhibition of Gal-3, we showed a significant decrease of GSC macropinocytosis activity, cell survival and invasion, in vitro and in vivo. Mechanistically, we demonstrate that Gal-3 binds to RAB10, a member of the RAS superfamily of small GTPases, and β1 integrin, which are both required for macropinocytosis activity and cell survival. Finally, by defining a Gal-3/macropinocytosis molecular signature, we could predict sensitivity to this dependency pathway and provide proof-of-principle for innovative therapeutic strategies to exploit this Achilles’ heel for a significant and unique subset of GBM patients.

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