Excessive release of neutrophil extracellular traps (NETs) has been reported in various human pathologies, including COVID-19 patients. Elevated NET levels serve as a biomarker, indicating increased coagulopathy and immunothrombosis risks in these patients. Traditional immunoassays employed to quantify NET release focus on bulk measurements of released chromatin in simplified microenvironments.
View Article and Find Full Text PDFIntestinal epithelial tight junction disruption is a primary contributing factor in alcohol-associated endotoxemia, systemic inflammation, and multiple organ damage. Ethanol and acetaldehyde disrupt tight junctions by elevating intracellular Ca. Here we identify TRPV6, a Ca-permeable channel, as responsible for alcohol-induced elevation of intracellular Ca, intestinal barrier dysfunction, and systemic inflammation.
View Article and Find Full Text PDFDuring the acute inflammatory response, the release of neutrophil extracellular traps (NETs) is a pro-inflammatory, preconditioning event on a biomaterial surface. Therefore, regulation of NET release through biomaterial design is one strategy to enhance biomaterial-guided in situ tissue regeneration. In this study, IgG adsorption on electrospun polydioxanone biomaterials with differing fiber sizes was explored as a regulator of in vitro human neutrophil NET release.
View Article and Find Full Text PDFSARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19. Individuals that develop severe manifestations have signs of dysregulated innate and adaptive immune responses.
View Article and Find Full Text PDFManuka honey, a topical wound treatment used to eradicate bacteria, resolve inflammation, and promote wound healing, is a focus in the tissue engineering community as a tissue template additive. However, its effect on neutrophil extracellular trap formation (NETosis) on a tissue engineering template has yet to be examined. As NETosis has been implicated in chronic inflammation and fibrosis, the reduction in this response within the wound environment is of interest.
View Article and Find Full Text PDFTissue Eng Part B Rev
April 2021
Biomaterial-guided tissue regeneration uses biomaterials to stimulate and guide the body's endogenous, regenerative processes to drive functional tissue repair and regeneration. To be successful, cell migration into the biomaterials is essential, which requires angiogenesis to maintain cell viability. Neutrophils, the first cells responding to an implanted biomaterial, are now known to play an integral part in angiogenesis in multiple tissues and exhibit considerable potential for driving angiogenesis in the context of tissue regeneration.
View Article and Find Full Text PDFManuka honey, a wound treatment used to eradicate bacteria, resolve inflammation, and promote wound healing, is a current focus in the tissue engineering community as a tissue template additive. However, Manuka honey's effect on neutrophils during the inflammation-resolving phase has yet to be examined. This study investigates the effect of 0.
View Article and Find Full Text PDFWe present evidence that protein citrullination, a proinflammatory and immune system-activating posttranslational modification (PTM) of arginine residues mediated by peptidyl arginine deiminases (PADs), is elevated in mouse models of retinal degenerations. Together with the fact that the animal models that we investigated (and their human counterparts) exhibit also anti-retinal autoantibodies, we propose that retinal citrullination is an immunogenic trigger that activates the immune system both locally and systemically, contributing to disease pathogenesis. Consistent with this possibility, we show that PAD compromise reduces the severity of Mertk-related retinal degeneration.
View Article and Find Full Text PDFNeutrophils, the first cells that interact with surface-adsorbed proteins on biomaterials, have been increasingly recognized as critical maestros in the foreign body response for guided tissue regeneration. Recent research has shown that small diameter (SD) fibers of electrospun tissue regeneration templates, which have a high surface area to volume ratio (SAVR), enhance the release of neutrophil extracellular traps (NETs) compared to large diameter (LD) fibers, resulting in impaired tissue regeneration. In this study, we evaluated the adsorption of eight human serum proteins on the surface of electrospun templates to investigate how protein adsorption may regulate the release of NETs.
View Article and Find Full Text PDFA large body of and evidence indicates that Manuka honey resolves inflammation and promotes healing when applied topically to a wound. In this study, the effect of two different concentrations (0.5% and 3% v/v) of Manuka honey on the release of cytokines, chemokines, and matrix-degrading enzymes from neutrophils was examined using a differentiated HL-60 cell line model in the presence of inflammatory stimuli.
View Article and Find Full Text PDFRecent work has shown that Manuka honey, an increasingly popular wound additive with potent antibacterial properties, also has anti-inflammatory properties. However, little research has been done examining its effect on neutrophils. This study investigates the hypothesis that Manuka honey reduces neutrophil superoxide release and chemotaxis and reduces the activation of the inflammatory nuclear factor-B (NF-B) signaling pathway under honey's cytotoxic limit.
View Article and Find Full Text PDFSince the discovery and definition of neutrophil extracellular traps (NETs) 14 years ago, numerous characteristics and physiological functions of NETs have been uncovered. Nowadays, the field continues to expand and novel mechanisms that orchestrate formation of NETs, their previously unknown properties, and novel implications in disease continue to emerge. The abundance of available data has also led to some confusion in the NET research community due to contradictory results and divergent scientific concepts, such as pro- and anti-inflammatory roles in pathologic conditions, demarcation from other forms of cell death, or the origin of the DNA that forms the NET scaffold.
View Article and Find Full Text PDFPurpose: Citrullination is a post-translational modification (PTM) that serves many normal physiological functions. Studies have shown that this PTM-along with expression of the catalyzing enzymes, peptidyl arginine deiminases (PADs)-are increased in autoimmune and age-related pathologies. PAD2 retinal expression has been previously documented in rat and human.
View Article and Find Full Text PDFUpon interaction, neutrophils can potentially release neutrophil extracellular traps (NETs) on the surface of an implanted electrospun template, which may be a significant preconditioning event for implantable biomaterials of yet unknown consequences. In this study, we investigated the potential of polydioxanone templates as a delivery vehicle for Cl-amidine, an inhibitor of peptidyl arginase deiminase 4 (PAD4), and if drug elution could attenuate PAD4-mediated NETosis in the vicinity of implanted templates. Electrospun polydioxanone templates were fabricated with distinct architectures, small diameter (0.
View Article and Find Full Text PDFDespite considerable recent progress in defining neutrophil functions and behaviors in tissue repair, much remains to be determined with regards to its overall role in the tissue integration of biomaterials. This article provides an overview of the neutrophil's numerous, important roles in both inflammation and resolution, and subsequently, their role in biomaterial integration. Neutrophils function in three primary capacities: generation of oxidative bursts, release of granules and formation of neutrophil extracellular traps (NETs); these combined functions enable neutrophil involvement in inflammation, macrophage recruitment, M2 macrophage differentiation, resolution of inflammation, angiogenesis, tumor formation and immune system activation.
View Article and Find Full Text PDFMounting evidence indicates that neutrophils, first responders to an implanted biomaterial, prime the microenvironment for recruited immune cells by secreting factors and releasing neutrophil extracellular traps (NETs) through NETosis. In this study, we investigated the role of electrospun template architecture and composition in regulating NETosis. Electrospun polydioxanone (PDO), collagen type I (COL), and blended PDO-COL templates (PC) were fabricated with small-diameter (0.
View Article and Find Full Text PDFWe report on a novel autoantigen expressed in human macular tissues, identified following an initial Western blot (WB)-based screening of sera from subjects with age-related macular degeneration (AMD) for circulating auto-antibodies (AAbs) recognizing macular antigens. Immunoprecipitation, 2D-gel electrophoresis (2D-GE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), direct enzyme-linked immunosorbent assays (ELISA), WBs, immunohistochemistry (IHC), human primary and ARPE-19 immortalized cell cultures were used to characterize this novel antigen. An approximately 40-kDa autoantigen in AMD was identified as the scavenger receptor CD5 antigen-like protein (CD5L), also known as apoptosis inhibitor of macrophage (AIM).
View Article and Find Full Text PDFBackground: The linkage between periodontal disease and rheumatoid arthritis is well established. Commonalities among the two are that both are chronic inflammatory diseases characterized by bone loss, an association with the shared epitope susceptibility allele, and anti-citrullinated protein antibodies.
Methods: To explore immune mechanisms that may connect the two seemingly disparate disorders, we measured host immune responses including T-cell phenotype and anti-citrullinated protein antibody production in human leukocyte antigen (HLA)-DR1 humanized C57BL/6 mice following exposure to the Gram-negative anaerobic periodontal disease pathogen Porphyromonas gingivalis.
PLoS One
June 2016
Background: We investigated sera from elderly subjects with and without age-related macular degeneration (AMD) for presence of autoantibodies (AAbs) against human macular antigens and characterized their identity.
Methods: Sera were collected from participants in the Age-Related Maculopathy Ancillary (ARMA) Study, a cross-sectional investigation ancillary to the Health ABC Study, enriched with participants from the general population. The resulting sample (mean age: 79.
Specificity for double-stranded DNA can arise due to somatic mutations within one of the branches of an autoreactive B cell clone. However, it is not known whether a different autospecificity predates anti-dsDNA and whether separate offshoots of an expanding B cell clone retain or evolve alternative specificities. We compared 3H9, an anti-dsDNA IgG, to 4H8 and 1A11, antibodies produced by hybridomas representing an alternative branch of the 3H9 B cell clone.
View Article and Find Full Text PDFDeficiencies in clearance of apoptotic cells predispose to the development of autoimmune disease. This is evident in mice lacking the receptor tyrosine kinases Tyro3, Axl, and Mer. Deficient mice exhibit an increased abundance of apoptotic cells in tissues and manifest diverse autoimmune conditions.
View Article and Find Full Text PDFThe specific modification of autoantigens and their redistribution into blebs at the surface of apoptotic cells contribute to the induction of autoimmune responses. Blebs containing fragments of the apoptotic nucleus separate from the remainder of the cell to form membrane-bound sub-cellular particles (SCPs), otherwise known as apoptotic bodies. To determine whether apoptotic bodies containing nuclear antigens represent a defined subset of SCPs, we examined the heterogeneity of particles generated by Jurkat cells following synchronization of the cell cycle by serum withdrawal and inhibition of topoisomerase I by camptothecin.
View Article and Find Full Text PDFFirm evidence links the process of apoptosis to the induction of autoimmune disease. However, questions remain regarding the precise interactions of dying cells with the immune system. Genetic analyses indicate that deficiencies in serum proteins or receptors that mediate clearance of apoptotic cells increase the risk of autoimmunity.
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