Organ-Specific Mechanisms of Transendothelial Neutrophil Migration in the Lung, Liver, Kidney, and Aorta

Maas, Sanne L.; Soehnlein, Oliver; Viola, Joana R.

doi:10.3389/fimmu.2018.02739

Cited by 111 publications

(117 citation statements)

References 272 publications

(336 reference statements)

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“…5 Glycosylation regulates leukocyte recruitment from the vasculature to most tissues, through the modulation of interactions between endothelial selectins and their ligands in leukocytes. 6,7 Deficiency in several glycosyltransferases involved in the biosynthesis of functional selectin ligands, as Galnt1, Gcnt1, B4galt1, Fut4, Fut7 and St3gal4, results in defective leukocyte recruitment [7][8][9] and in homeostatic alterations, namely pronounced blood neutrophilia. 10,11 Selectin ligands are commonly decorated with O-glycans bearing a terminal sialyl Lewis x (sLe x ) (sialic acid α2,3Galβ1-4 (Fucα1,3) GlcNAc-R) epitope.…”

Section: Introductionmentioning

confidence: 99%

Deficiency in the glycosyltransferase Gcnt1 increases susceptibility to tuberculosis through a mechanism involving neutrophils

et al. 2020

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Modulation of immunity and disease by glycans is increasingly recognized. However, how host glycosylation shapes and is shaped by tuberculosis remains poorly understood. We show that deficiency in the glucosaminyl (N-acetyl) transferase 1 (Gcnt1), a key enzyme for core-2 O-glycans biosynthesis, drives susceptibility to Mycobacterium tuberculosis infection. The increased susceptibility of Gcnt1 deficient mice was characterized by extensive lung immune pathology, mechanistically related to neutrophils. Uninfected Gcnt1 deficient mice presented bone marrow, blood and lung neutrophilia, which further increased with infection. Blood neutrophilia required Gcnt1 deficiency in the hematopoietic compartment, relating with enhanced granulopoiesis, but normal cellular egress from the bone marrow. Interestingly, for the blood neutrophilia to translate into susceptibility to M. tuberculosis infection, Gnct1 deficiency in the stroma was also necessary. Complete Gcnt1 deficiency associated with increased lung expression of the neutrophil chemoattractant CXCL2. Lastly, we demonstrate that the transcript levels of various glycosyltransferase-encoding genes were altered in whole blood of active tuberculosis patients and that sialyl Lewis x, a glycan widely present in human neutrophils, was detected in the lung of tuberculosis patients. Our findings reveal a previously unappreciated link between Gcnt1, neutrophilia and susceptibility to M. tuberculosis infection, uncovering new players balancing the immune response in tuberculosis.

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Section: Introductionmentioning

confidence: 99%

Deficiency in the glycosyltransferase Gcnt1 increases susceptibility to tuberculosis through a mechanism involving neutrophils

et al. 2020

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“…The decrease of CXCR2 expression on the cell surface of neutrophils is among the mechanisms leading to this failure. The prolonged exposure to CXCR2 agonists, which leads to phosphorylation of G protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) and induces the desensitization and internalization of CXCR2, can explain the down-regulation of this receptor [16]. In addition, the activation of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) by inflammatory products, such as C-reactive protein (CRP), bacterial products, apoptotic cells, or activated platelets, can also account for CXCR2 neutrophil endocytosis [12,19].…”

Section: Introductionmentioning

confidence: 99%

Neutrophil Function Impairment Is a Host Susceptibility Factor to Bacterial Infection in Diabetes

Insuela¹,

Coutinho²,

Martins³

et al. 2020

Cells of the Immune System

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Diabetes mellitus is a highly prevalent noncommunicable disease globally. One of the main complications of diabetes is the increased susceptibility to bacterial infection. Neutrophils play a crucial role in inflammatory response against bacterial infections, once they are the first cells recruited to the sites of injury. In diabetes, there is a failure in the neutrophil functions, including migration, ROS production, phagocytosis, and bacterial killing, which are associated with the high incidence of bacterial infections. Herein, we point out pieces of evidence revealing the primary molecular mechanisms involved with impairment of neutrophil functions in diabetes, with relationship with high susceptibility to bacterial infections.

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“…In this study, we demonstrate that RSPO2 deletion in adult mice results in the aberrant presence of neutrophils in the luminal space of the lung. Recognizing that lung neutrophils are normally restricted to capillaries and are activated and recruited into the interstitium or the alveolar parenchyma due to endothelial stress/damage (12), our study further demonstrates significant lung barrier dysfunction in RSPO2 −/− mice, suggesting that tonic RSPO2 expression is required for normal barrier function.…”

Section: Introductionmentioning

confidence: 60%

R-spondin 2 mediates neutrophil egress into the alveolar space through increased lung permeability.

Jackson

Costa

Pastore

et al. 2019

Preprint

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Objective: R-spondin 2 (RSPO2) is required for proper lung morphogenesis. Our objective was to investigate whether RSPO2 is similarly important in homeostasis of the adult lung. Unexpectedly, we observed changes in neutrophil migration and lung vascular permeability in RSPO2-deficient (RSPO2 -/-) mice compared to RSPO2 control (RSPO2 +/+ ) mice, independent of experimental injury/challenge.Here we use multiple methods to quantify these observations to further understand how tonic RSPO2 expression regulates lung homeostasis.Results: Quantitative PCR (qPCR) analysis demonstrated significantly higher myeloperoxidase (MPO) expression in bronchoalveolar lavage fluid (BALF) cell content from RSPO2 -/mice compared to RSPO2 +/+ mice. Immunocytochemical (ICC) analysis likewise demonstrated significantly more MPO+ cells in BALF from RSPO2 -/mice compared to RSPO2 +/+ mice, confirming the increase of infiltrated neutrophils. We then assessed lung permeability/barrier disruption via Fluorescein isothiocyanate (FITC)-dextran instillation and found a significantly higher dextran concentration in the plasma of RSPO2 -/mice compared to identically treated RSPO2 +/+ mice. These data demonstrate that RSPO2 may be crucial for lung barrier integrity and can facilitate an increase in neutrophil migration from circulation into alveolar spaces due to increased lung permeability/barrier disruption. Our studies suggest additional research is needed to evaluate RSPO2 in scenarios exhibiting either pulmonary edema or neutrophilia.

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Organ-Specific Mechanisms of Transendothelial Neutrophil Migration in the Lung, Liver, Kidney, and Aorta

Cited by 111 publications

References 272 publications

Deficiency in the glycosyltransferase Gcnt1 increases susceptibility to tuberculosis through a mechanism involving neutrophils

Deficiency in the glycosyltransferase Gcnt1 increases susceptibility to tuberculosis through a mechanism involving neutrophils

Neutrophil Function Impairment Is a Host Susceptibility Factor to Bacterial Infection in Diabetes

R-spondin 2 mediates neutrophil egress into the alveolar space through increased lung permeability.

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