X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Priming of Neutrophils and Differentiated PLB-985 Cells by Pathophysiological Concentrations of TNF-α Is Partially Oxygen Dependent
    S. Karger AG ; 2011
    In:  Journal of Innate Immunity Vol. 3, No. 3 ( 2011), p. 298-314
    Details
    In: Journal of Innate Immunity, S. Karger AG, Vol. 3, No. 3 ( 2011), p. 298-314
    Abstract: Activation of polymorphonuclear leukocytes (PMN) can be modulated to intermediate ‘primed’ states characterized by enhanced responsiveness to subsequent stimuli. We studied priming in response to TNF-α in human PMN and PLB-985 cells, a myeloid cell line differentiated to a neutrophilic phenotype (PLB-D). PMN generated reactive oxygen species (ROS) in response to TNF-α alone, and NADPH oxidase activity increased in response to stimulation with formyl-Met-Leu-Phe after priming. PLB-D cells also demonstrated priming of NADPH oxidase activity. Similar to priming by endotoxin, priming of the respiratory burst by TNF-α was predominantly oxygen dependent, with marked attenuation of ROS generation if primed anaerobically. Both PMN and PLB-D cells displayed significant increases in cell surface CD11b and gp91 〈 sup 〉 phox 〈 /sup 〉 expression after TNF-α priming and PMN displayed activation of MAPK. In response to TNF-α priming, neither mobilization of intracellular proteins nor activation of MAPK pathways was NADPH oxidase dependent. Priming of PMN and PLB-D cells by low TNF-α concentrations enhanced chemotaxis. These data demonstrate that pathophysiological concentrations of TNF-α elicit NADPH oxidase-derived ROS and prime cells for enhanced surface protein expression, activation of p38 and ERK1/2 MAPK pathways, and increased chemotaxis. Furthermore, PLB-D cells undergo TNF-α priming and provide a genetically modifiable model to study priming mechanisms.
    Type of Medium: Online Resource
    ISSN: 1662-811X , 1662-8128
    URL: Article
    DOI: 10.1159/000321439
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2011
    detail.hit.zdb_id: 2455818-7
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 2
    Online Resource
    Online Resource
    Neutrophil Phenotype Correlates With Postoperative Inflammatory Outcomes in Infants Undergoing Cardiopulmonary Bypass
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Pediatric Critical Care Medicine Vol. 18, No. 12 ( 2017-12), p. 1145-1152
    Details
    In: Pediatric Critical Care Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 18, No. 12 ( 2017-12), p. 1145-1152
    Abstract: Infants with congenital heart disease frequently require cardiopulmonary bypass, which causes systemic inflammation. The goal of this study was to determine if neutrophil phenotype and activation status predicts the development of inflammatory complications following cardiopulmonary bypass. Design: Prospective cohort study. Setting: Tertiary care PICU with postoperative cardiac care. Patients: Thirty-seven patients 5 days to 10 months old with congenital heart disease requiring cardiopulmonary bypass. Interventions: None. Measurements and Main Results: Laboratory and clinical data collected included length of mechanical ventilation, acute kidney injury, and fluid overload. Neutrophils were isolated from whole blood at three time points surrounding cardiopulmonary bypass. Functional analyses included measurement of cell surface protein expression and nicotinamide adenine dinucleotide phosphate oxidase activity. Of all patients studied, 40.5% displayed priming of nicotinamide adenine dinucleotide phosphate oxidase activity in response to N-formyl-Met-Leu-Phe stimulation 24 hours post cardiopulmonary bypass as compared to pre bypass. Neonates who received steroids prior to bypass demonstrated enhanced priming of nicotinamide adenine dinucleotide phosphate oxidase activity at 48 hours. Patients who displayed priming post cardiopulmonary bypass were 8.8 times more likely to develop severe acute kidney injury as compared to nonprimers. Up-regulation of neutrophil surface CD11b levels pre- to postbypass occurred in 51.4% of patients, but this measure of neutrophil priming was not associated with acute kidney injury. Subsequent analyses of the basal neutrophil phenotype revealed that those with higher basal CD11b expression were significantly less likely to develop acute kidney injury. Conclusions: Neutrophil priming occurs in a subset of infants undergoing cardiopulmonary bypass. Acute kidney injury was more frequent in those patients who displayed priming of nicotinamide adenine dinucleotide phosphate oxidase activity after cardiopulmonary bypass. This pilot study suggests that neutrophil phenotypic signature could be used to predict inflammatory organ dysfunction.
    Type of Medium: Online Resource
    ISSN: 1529-7535
    URL: Article
    DOI: 10.1097/PCC.0000000000001361
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2070997-3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 3
    Online Resource
    Online Resource
    Novel neutrophil phenotypic signature in pediatric patients with type 1 diabetes and diabetic ketoacidosis
    Oxford University Press (OUP) ; 2022
    In:  Journal of Leukocyte Biology Vol. 111, No. 4 ( 2022-03-25), p. 849-856
    Details
    In: Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 111, No. 4 ( 2022-03-25), p. 849-856
    Abstract: Type 1 diabetes (T1D) is a chronic inflammatory condition sometimes complicated by acute diabetic ketoacidosis (DKA). A subset of patients with T1D develop DKA independent of known risk factors. This study tested the hypothesis that circulating polymorphonuclear leukocytes (PMN) from children with T1D and DKA would exhibit a primed phenotype and that the signature would be unique in patients predisposed to have DKA. Using a prospective cohort study design, neutrophil phenotype was assessed in 30 patients with T1D seen in endocrinology clinic for routine care, 30 patients with acute DKA, and 36 healthy donors. Circulating PMN from patients with DKA display a primed phenotype with increased basal cell-surface CD11b, l-selectin shedding, and enhanced fMLF-elicited reactive oxygen species (ROS) production. Moreover, PMN from T1D patients both with and without DKA lack the capacity to be further primed by incubation with TNF-α, a classic priming stimulus. Primed PMN phenotypic signatures demonstrated are independent of hemoglobin A1c, the premier biological marker for DKA risk, and are consistent with a hyperinflammatory state. A single nucleotide polymorphism in TLR-1 (1805G & gt;T), known to be associated with a hyperinflammatory PMN phenotype, correlated with DKA. This study elucidated a novel phenotypic signature in circulating PMN from children with T1D with and without DKA, and suggests the possibility of a previously unrecognized PMN phenotype with potential clinical implications. Immunophenotype and genotype may be applicable as biomarkers for DKA risk stratification in patients with T1D.
    Type of Medium: Online Resource
    ISSN: 0741-5400 , 1938-3673
    URL: Article
    DOI: 10.1002/JLB.3A1220-826R
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2026833-6
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 4
    Online Resource
    Online Resource
    Neutrophil azurophilic granule exocytosis is primed by TNF-α and partially regulated by NADPH oxidase
    SAGE Publications ; 2016
    In:  Innate Immunity Vol. 22, No. 8 ( 2016-11), p. 635-646
    Details
    In: Innate Immunity, SAGE Publications, Vol. 22, No. 8 ( 2016-11), p. 635-646
    Abstract: Neutrophil (polymorphonuclear leukocyte) activation with release of granule contents plays an important role in the pathogenesis of acute lung injury, prompting clinical trials of inhibitors of neutrophil elastase. Despite mounting evidence for neutrophil-mediated host tissue damage in a variety of disease processes, mechanisms regulating azurophilic granule exocytosis at the plasma membrane, and thus release of elastase and other proteases, are poorly characterized. We hypothesized that azurophilic granule exocytosis would be enhanced under priming conditions similar to those seen during acute inflammatory events and during chronic inflammatory disease, and selected the cytokine TNF-α to model this in vitro. Neutrophils stimulated with TNF-α alone elicited intracellular reactive oxygen species (ROS) generation and mobilization of secretory vesicles, specific, and gelatinase granules. p38 and ERK1/2 MAPK were involved in these components of priming. TNF-α priming alone did not mobilize azurophilic granules to the cell surface, but did markedly increase elastase release into the extracellular space in response to secondary stimulation with N-formyl-Met-Leu-Phe (fMLF). Priming of fMLF-stimulated elastase release was further augmented in the absence of NADPH oxidase-derived ROS. Our findings provide a mechanism for host tissue damage during neutrophil-mediated inflammation and suggest a novel anti-inflammatory role for the NADPH oxidase.
    Type of Medium: Online Resource
    ISSN: 1753-4259 , 1753-4267
    URL: Article
    DOI: 10.1177/1753425916668980
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2016
    detail.hit.zdb_id: 2381250-3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 5
    Online Resource
    Online Resource
    Evaluation of hematologic variables in newborn C57/ BL 6 mice up to day 35
    Wiley ; 2016
    In:  Veterinary Clinical Pathology Vol. 45, No. 1 ( 2016-03), p. 87-95
    Details
    In: Veterinary Clinical Pathology, Wiley, Vol. 45, No. 1 ( 2016-03), p. 87-95
    Abstract: Hematologic variables are often analyzed in animal analogs during the investigation of complex disease etiologies such as necrotizing enterocolitis. However, reference intervals ( RI ) can vary depending on animal strain, age, and sampling site. Reference intervals have been published for adult C57 BL /6J mice, but not newborn C57 BL /6J mice. Objectives The purpose of the present study was to determine hematologic RI in newborn C57 BL /6J mice up to day 35. Methods C57 BL /6J mice founders from The Jackson Laboratory were bred at the University of Iowa. Blood samples were obtained via facial vein sampling at postnatal days 0 (p0), p7, p14, p21, p28, or young adulthood (p35). CBC s were determined with the Sysmex XT ‐2000iV analyzer within 30 minutes of blood collection at a 1:10 dilution. Statistics were determined using nonparametric methods following ASVCP guidelines. Results Hematologic RI were determined for each of the 6 groups ( n = 247, n ≥ 39 per group). Significantly higher values for HGB , RBC , and PLT counts were observed with advancing developmental age. Total WBC counts remained relatively stable during the first 35 days of life. However, WBC differential counts were dominated by neutrophils and lymphocytes in the younger mice, with a trend toward a lymphocytic leukogram on day 35. Conclusions These results illustrate the dynamic changes in hematologic variables during murine development after birth. Utilization of age‐specific RI is advised when evaluating data derived from experimental perinatal mouse models.
    Type of Medium: Online Resource
    ISSN: 0275-6382 , 1939-165X
    URL: Issue
    URL: Article
    DOI: 10.1111/vcp.2016.45.issue-1
    DOI: 10.1111/vcp.12314
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2114702-4
    SSG: 22
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 6
    Online Resource
    Online Resource
    Evaluation of an association between RANKL and OPG with bone disease in people with cystic fibrosis
    Elsevier BV ; 2023
    In:  Journal of Cystic Fibrosis Vol. 22, No. 1 ( 2023-01), p. 140-145
    Details
    In: Journal of Cystic Fibrosis, Elsevier BV, Vol. 22, No. 1 ( 2023-01), p. 140-145
    Type of Medium: Online Resource
    ISSN: 1569-1993
    URL: Article
    DOI: 10.1016/j.jcf.2022.08.011
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2091075-7
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 7
    Online Resource
    Online Resource
    Francisella tularensis directly interacts with the endothelium and recruits neutrophils with a blunted inflammatory phenotype
    American Physiological Society ; 2009
    In:  American Journal of Physiology-Lung Cellular and Molecular Physiology Vol. 296, No. 6 ( 2009-06), p. L1076-L1084
    Details
    In: American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, Vol. 296, No. 6 ( 2009-06), p. L1076-L1084
    Abstract: Francisella tularensis, the causative agent of tularemia, is a highly virulent organism, especially when exposure occurs by inhalation. Recent data suggest that Francisella interacts directly with alveolar epithelial cells. Although F. tularensis causes septicemia and can live extracellularly in a murine infection model, there is little information about the role of the vascular endothelium in the host response. We hypothesized that F. tularensis would interact with pulmonary endothelial cells as a prerequisite to the clinically observed recruitment of neutrophils to the lung. Using an in vitro Transwell model system, we studied interactions between F. tularensis live vaccine strain ( Ft LVS) and a pulmonary microvascular endothelial cell (PMVEC) monolayer. Organisms invaded the endothelium and were visualized within individual endothelial cells by confocal microscopy. Although these bacteria-endothelial cell interactions did not elicit production of the proinflammatory chemokines, polymorphonuclear leukocytes (PMN) were stimulated to transmigrate across the endothelium in response to Ft LVS. Moreover, transendothelial migration altered the phenotype of recruited PMN; i.e., the capacity of these PMN to activate NADPH oxidase and release elastase in response to subsequent stimulation was reduced compared with PMN that traversed PMVEC in response to Streptococcus pneumoniae. The blunting of PMN responsiveness required PMN transendothelial migration but did not require PMN uptake of Ft LVS, was not dependent on the presence of serum-derived factors, and was not reproduced by Ft LVS-conditioned medium. We speculate that the capacity of Ft LVS-stimulated PMVEC to support transendothelial migration of PMN without triggering release of IL-8 and monocyte chemotactic protein-1 and to suppress the responsiveness of transmigrated PMN to subsequent stimulation could contribute to the dramatic virulence during inhalational challenge with Francisella.
    Type of Medium: Online Resource
    ISSN: 1040-0605 , 1522-1504
    URL: Article
    DOI: 10.1152/ajplung.90332.2008
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2009
    detail.hit.zdb_id: 1477300-4
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 8
    Online Resource
    Online Resource
    Endotoxin Priming of Neutrophils Requires NADPH Oxidase-generated Oxidants and Is Regulated by the Anion Transporter ClC-3
    Elsevier BV ; 2007
    In:  Journal of Biological Chemistry Vol. 282, No. 47 ( 2007-11), p. 33958-33967
    Details
    In: Journal of Biological Chemistry, Elsevier BV, Vol. 282, No. 47 ( 2007-11), p. 33958-33967
    Type of Medium: Online Resource
    ISSN: 0021-9258
    URL: Article
    DOI: 10.1074/jbc.M705289200
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2007
    detail.hit.zdb_id: 2141744-1
    detail.hit.zdb_id: 1474604-9
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 9
    Online Resource
    Online Resource
    Lipoproteins from Staphylococcus aureus Drive Neutrophil Extracellular Trap Formation in a TLR2/1- and PAD-Dependent Manner
    The American Association of Immunologists ; 2021
    In:  The Journal of Immunology Vol. 207, No. 3 ( 2021-08-01), p. 966-973
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 207, No. 3 ( 2021-08-01), p. 966-973
    Abstract: Neutrophils, polymorphonuclear leukocytes (PMN), play a critical role in the innate immune response to Staphylococcus aureus, a pathogen that continues to be associated with significant morbidity and mortality. Neutrophil extracellular trap (NET) formation is involved in ensnaring and killing of S. aureus, but this host–pathogen interaction also leads to host tissue damage. Importantly, NET components including neutrophil proteases are under consideration as therapeutic targets in a variety of disease processes. Although S. aureus lipoproteins are recognized to activate cells via TLRs, specific mechanisms of interaction with neutrophils are poorly delineated. We hypothesized that a lipoprotein-containing cell membrane preparation from methicillin-resistant S. aureus (MRSA-CMP) would elicit PMN activation, including NET formation. We investigated MRSA-CMP–elicited NET formation, regulated elastase release, and IL-8 production in human neutrophils. We studied PMN from healthy donors with or without a common single-nucleotide polymorphism in TLR1, previously demonstrated to impact TLR2/1 signaling, and used cell membrane preparation from both wild-type methicillin-resistant S. aureus and a mutant lacking palmitoylated lipoproteins (lgt). MRSA-CMP elicited NET formation, elastase release, and IL-8 production in a lipoprotein-dependent manner. TLR2/1 signaling was involved in NET formation and IL-8 production, but not elastase release, suggesting that MRSA-CMP–elicited elastase release is not mediated by triacylated lipoproteins. MRSA-CMP also primed neutrophils for enhanced NET formation in response to a subsequent stimulus. MRSA-CMP–elicited NET formation did not require Nox2-derived reactive oxygen species and was partially dependent on the activity of peptidyl arginine deiminase (PAD). In conclusion, lipoproteins from S. aureus mediate NET formation via TLR2/1 with clear implications for patients with sepsis.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.2100283
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2021
    detail.hit.zdb_id: 1475085-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 10
    Online Resource
    Online Resource
    Mycobacterium tuberculosis Lipoarabinomannan Activates Human Neutrophils via a TLR2/1 Mechanism Distinct from Pam3CSK4
    The American Association of Immunologists ; 2020
    In:  The Journal of Immunology Vol. 204, No. 3 ( 2020-02-01), p. 671-681
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 204, No. 3 ( 2020-02-01), p. 671-681
    Abstract: Neutrophils, polymorphonuclear (PMN) leukocytes, play an important role in the early innate immune response to Mycobacterium tuberculosis infection in the lung. Interactions between PMN and mycobacterial lipids impact the activation state of these migrated cells with consequences for the surrounding tissue in terms of resolution versus ongoing inflammation. We hypothesized that lipoarabinomannan from M. tuberculosis (Mtb LAM) would prime human PMN in a TLR2-dependent manner and investigated this with specific comparison with the purified synthetic TLR2 agonists, Pam3CSK4 and FSL-1. In contrast to Pam3CSK4 and FSL-1, we found Mtb LAM did not induce any of the classical PMN priming phenotypes, including enhancement of NADPH oxidase activity, shedding of l-selectin, or mobilization of CD11b. However, exposure of PMN to Mtb LAM did elicit pro- and anti-inflammatory cytokine production and release in a TLR2/1-dependent manner, using the TLR1 single-nucleotide polymorphism rs5743618 (1805G/T) as a marker for TLR2/1 specificity. Moreover, Mtb LAM did not elicit p38 MAPK phosphorylation or endocytosis, although these processes occurred with Pam3CSK4 stimulation, and were necessary for the early priming events to occur. Interestingly, Mtb LAM did not abrogate priming responses elicited by Pam3CSK4. Notably, subfractionation of light membranes from Pam3CSK4 versus Mtb LAM–stimulated cells demonstrated differential patterns of exocytosis. In summary, Mtb LAM activates PMN via TLR2/1, resulting in the production of cytokines but does not elicit early PMN priming responses, as seen with Pam3CSK4. We speculate that the inability of Mtb LAM to prime PMN may be due to differential localization of TLR2/1 signaling.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.1900919
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2020
    detail.hit.zdb_id: 1475085-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
Nothing or not found what you are looking for? Please check your search query or use the Interlibrary Loan Search.
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages