Regulation of Neutrophil Apoptosis Differs after in vivo Transmigration to Skin Chambers and Synovial Fluid: A Role for Inflammasome-Dependent Interleukin-1β Release

Christenson, Karin; Björkman, Lena; Karlsson, Anna; Bylund, Johan

doi:10.1159/000350378

Cited by 22 publications

(19 citation statements)

References 29 publications

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“…Included synovial fluids were centrifuged and pellets resuspended in KRG and stored on melting ice until use. Viability of freshly prepared synovial fluid neutrophils was around 90% as has been previously reported …”

Section: Methodssupporting

confidence: 80%

Neutrophil recruitment to inflamed joints can occur without cellular priming

Björkman

Christenson

Davidsson

et al. 2018

Journal of Leukocyte Biology

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Recruitment of neutrophils from blood to tissues is a cardinal event in inflammation during which neutrophils switch from a resting, naive state to a preactivated, primed phenotype; the priming process is characterized by alterations in the composition of cell surface adhesins, for example, shedding of l‐selectin and mobilization of granule‐stored integrins to the cell surface. Ligation of chemotactic receptors and interactions with the endothelial lining are established triggers of neutrophil priming and in line with this, in vivo transmigrated neutrophils obtained from tissues are typically highly primed. We here characterize the priming of neutrophils brought about by in vivo recruitment from blood to inflamed joints by the analyses of synovial fluid and blood from patients with inflammatory arthritis. For comparisons, we used controlled in vivo models of neutrophil transmigration to skin of healthy subjects. In contrast to the residing view and in vivo transmigrated neutrophils from skin models, neutrophils from synovial fluid were often surprisingly resting and phenotypically very similar to naive cells isolated from peripheral blood; synovial fluid cells often retained l‐selectin and had undergone minimal up‐regulation of integrin receptors. In complete agreement with our in vivo findings, cell‐free synovial fluid was potently chemotactic without triggering alteration of surface receptors also in vitro. We conclude that tissue recruitment of neutrophils does not by default trigger l‐selectin shedding and granule mobilization, and the chemoattractant(s) guiding neutrophils to synovial fluid apparently operate without inducing cellular priming.

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Section: Methodssupporting

confidence: 80%

Neutrophil recruitment to inflamed joints can occur without cellular priming

Björkman

Christenson

Davidsson

et al. 2018

Journal of Leukocyte Biology

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“…[47,48]. We and others have shown previously that joint-derived T regs have suppressive capacity in vitro [23,24], but it is possible that in the presence of IL-1b, which is present in the rheumatic joint [49], regulatory T cells expressing the receptor for this cytokine could transiently lose their suppressive activity.…”

Section: Discussionmentioning

confidence: 97%

IL-1R1 is expressed on both Helios+ and Helios−FoxP3+CD4+ T cells in the rheumatic joint

Müller

Herrath

Malmström

2015

Clinical and Experimental Immunology

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SummarySynovial fluid from rheumatic joints displays a well-documented enrichment of forkhead box protein 3 (FoxP3)1 regulatory T cells (tissue We also demonstrate a striking enrichment of IL-1R1 expression in synovial CD4 1 T cells that was restricted to the CD25-expressing FoxP3 population, but independent of Helios. IL-1R1 expression appears to define a tissue T reg cell phenotype together with the expression of CD25, glucocorticoid-induced TNF receptor family-related gene (GITR) and CTLA-4.

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“…Prolonged survival of ARDS alv PMNs has been reported previously and attributed to GM-CSF and/or granulocyte colony-stimulating factor in BALF (23); however, in contrast to Matute-Bello and colleagues, we did not observe significantly elevated levels of these cytokines, perhaps related to disease heterogeneity and differences in sampling time. Delayed apoptosis has been measured in neutrophils recruited to skin chambers versus paired circulating neutrophils, but synovial fluid-derived PMNs from patients with rheumatoid arthritis exhibited normal apoptosis (45). These differences correlated with Chemiluminescence was recorded using a Centro LB 960 luminometer and expressed graphically as the absolute peak height in relative light units.…”

Section: Discussionmentioning

confidence: 99%

Acute Respiratory Distress Syndrome Neutrophils Have a Distinct Phenotype and Are Resistant to Phosphoinositide 3-Kinase Inhibition

Juss

House²,

Amour³

et al. 2016

Am J Respir Crit Care Med

125

136

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Rationale: Acute respiratory distress syndrome is refractory to pharmacological intervention. Inappropriate activation of alveolar neutrophils is believed to underpin this disease's complex pathophysiology, yet these cells have been little studied.Objectives: To examine the functional and transcriptional profiles of patient blood and alveolar neutrophils compared with healthy volunteer cells, and to define their sensitivity to phosphoinositide 3-kinase inhibition.Methods: Twenty-three ventilated patients underwent bronchoalveolar lavage. Alveolar and blood neutrophil apoptosis, phagocytosis, and adhesion molecules were quantified by flow cytometry, and oxidase responses were quantified by chemiluminescence. Cytokine and transcriptional profiling were used in multiplex and GeneChip arrays.Measurements and Main Results: Patient blood and alveolar neutrophils were distinct from healthy circulating cells, with increased CD11b and reduced CD62L expression, delayed constitutive apoptosis, and primed oxidase responses. Incubating control cells with disease bronchoalveolar lavage recapitulated the aberrant functional phenotype, and this could be reversed by phosphoinositide 3-kinase inhibitors. In contrast, the prosurvival phenotype of patient cells was resistant to phosphoinositide 3-kinase inhibition. RNA transcriptomic analysis revealed modified immune, cytoskeletal, and cell death pathways in patient cells, aligning closely to sepsis and burns datasets but not to phosphoinositide 3-kinase signatures.Conclusions: Acute respiratory distress syndrome blood and alveolar neutrophils display a distinct primed prosurvival profile and transcriptional signature. The enhanced respiratory burst was phosphoinositide 3-kinase-dependent but delayed apoptosis and the altered transcriptional profile were not. These unexpected findings cast doubt over the utility of phosphoinositide 3-kinase inhibition in acute respiratory distress syndrome and highlight the importance of evaluating novel therapeutic strategies in patient-derived cells.

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Regulation of Neutrophil Apoptosis Differs after in vivo Transmigration to Skin Chambers and Synovial Fluid: A Role for Inflammasome-Dependent Interleukin-1β Release

Cited by 22 publications

References 29 publications

Neutrophil recruitment to inflamed joints can occur without cellular priming

Neutrophil recruitment to inflamed joints can occur without cellular priming

IL-1R1 is expressed on both Helios+ and Helios−FoxP3+CD4+ T cells in the rheumatic joint

Acute Respiratory Distress Syndrome Neutrophils Have a Distinct Phenotype and Are Resistant to Phosphoinositide 3-Kinase Inhibition

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