Neutrophil dysfunction due to continuous mechanical shear exposure in mechanically assisted circulation in vitro

2021 ◽  
Author(s):  
Wenji Sun ◽  
Jiafeng Zhang ◽  
Aakash Shah ◽  
Katherin Arias ◽  
Zachary Berk ◽  
...  
Keyword(s):  
Assisted Circulation ◽  
Neutrophil Dysfunction

scholarly journals Bactericidal/Permeability-Increasing Protein Preeminently Mediates Clearance of Pseudomonas aeruginosa In Vivo via CD18-Dependent Phagocytosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jomkuan Theprungsirikul ◽  
Sladjana Skopelja-Gardner ◽  
Ashley S. Burns ◽  
Rachel M. Wierzbicki ◽  
William F. C. Rigby
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Critical Role ◽  
Chronic Obstructive ◽  
Dependent Manner ◽  
Opsonic Activity ◽  
Obstructive Pulmonary Disease ◽  
Neutrophil Dysfunction ◽  
Chronic Lung Infection

Chronic Pseudomonas aeruginosa infection mysteriously occurs in the airways of patients with cystic fibrosis (CF), bronchiectasis (BE), and chronic obstructive pulmonary disease (COPD) in the absence of neutrophil dysfunction or neutropenia and is strongly associated with autoimmunity to bactericidal permeability-increasing protein (BPI). Here, we define a critical role for BPI in in vivo immunity against P. aeruginosa. Wild type and BPI-deficient (Bpi-/-) mice were infected with P. aeruginosa, and bacterial clearance, cell infiltrates, cytokine production, and in vivo phagocytosis were quantified. Bpi-/- mice exhibited a decreased ability to clear P. aeruginosa in vivo in concert with increased neutrophil counts and cytokine release. Bpi-/- neutrophils displayed decreased phagocytosis that was corrected by exogenous BPI in vitro. Exogenous BPI also enhanced clearance of P. aeruginosa in Bpi-/- mice in vivo by increasing P. aeruginosa uptake by neutrophils in a CD18-dependent manner. These data indicate that BPI plays an essential role in innate immunity against P. aeruginosa through its opsonic activity and suggest that perturbations in BPI levels or function may contribute to chronic lung infection with P. aeruginosa.

scholarly journals Frailty Is Associated With Neutrophil Dysfunction Which Is Correctable With Phosphoinositol-3-Kinase Inhibitors

2020 ◽  
Vol 75 (12) ◽  
pp. 2320-2325
Author(s):  
Daisy Wilson ◽  
William Drew ◽  
Alice Jasper ◽  
Helena Crisford ◽  
Peter Nightingale ◽  
...  
Keyword(s):  
Older Adults ◽  
Systemic Inflammation ◽  
Kinase Inhibitors ◽  
Frailty Index ◽  
Neutrophil Migration ◽  
Neutrophil Function ◽  
Community Dwelling ◽  
The United Kingdom ◽  
Neutrophil Dysfunction

Abstract Neutrophil dysfunction has been described with age, appears exaggerated in infection, with altered phosphoinositol signaling a potential mechanism. However, functional aging is heterogeneous. Frailty is a negative health status and is more common in older adults. We hypothesized that neutrophil migration may be compromised in frailty, associated with the degree of frailty experienced by the older person. We compared measures of frailty, neutrophil function, and systemic inflammation in 40 young and 77 older community-dwelling adults in the United Kingdom. Systemic neutrophils exhibited an age-associated reduction in the accuracy of migration (chemotaxis) which was further blunted with frailty. The degree of migratory inaccuracy correlated with physical (adjusted hand grip strength) and cognitive (Stroop test) markers of frailty. Regression analysis demonstrated that age, Charlson comorbidity index, and frailty index were able to predict neutrophil chemotaxis. Reduced chemotaxis of neutrophils from frail adults could be reversed using selective PI3K inhibitors. Exposure of neutrophils from young adults to plasma from chronically inflamed frail older adults could not recapitulate the migratory deficit in vitro, and there were no relationships with systemic inflammation and neutrophil dysfunction. Frailty exaggerated the neutrophil deficits seen with advanced age but aspects of the frailty-associated deficit in neutrophil function are rescuable and thus potentially form a therapeutic target to improve outcomes from infection in older adults.

Hemolysis induced by a Bellofram blood pump; chronic in vitro evaluation

1965 ◽  
Vol 20 (2) ◽  
pp. 339-342 ◽  
Author(s):  
Harold V. Liddle ◽  
Harold C. Reynolds ◽  
Warner W. Carlson
Keyword(s):  
Assisted Circulation ◽  
Free Hemoglobin ◽  
Plasma Hemoglobin ◽  
Hourly Rate ◽  
Priming Volume ◽  
Normal Human ◽  
Dog Blood ◽  
Reciprocating Pump ◽  
Free Plasma

In the application of extracorporeal pumping systems to chronic assisted circulation, hemolysis may be an important factor. A reciprocating pump utilizing rolling diaphragms has been tested for production of free plasma hemoglobin. In a recirculating system, 1,500 ml of freshly drawn heparinized dog blood was circulated at a flow rate of 3,000 ml/min against pressures of 100, 200, and 300 mm Hg for from 1 to 24 hr. Hemolysis was determined by a modified benzidine method. Recirculation for 1 hr against a height of 142 cm produced 3.6 mg/100 ml, 1.8 mg/100 ml, and 2.4 mg/100 ml free plasma hemoglobin, respectively, for hemolysis indices of 0.001- 0.0013. When the same priming volume was recirculated at 3,000 ml/min and 300 mm Hg pressure for 24 hr, the average hourly rate of free hemoglobin accumulation was 0.5 mg/100 ml, an index of 0.0006. These rates of hemolysis are comparable to the estimated normal human production of free plasma hemoglobin. The extremely low rate of hemolysis produced by this pump is related to the noncompressive action of the rolling diaphragms and flap valves. The characteristics of its performance make this pump ideally suited to chronic perfusion. extracorporeal pump; assisted circulation; rolling diaphragm; reciprocating pump Submitted on June 18, 1964

Recombinant human granulocyte colony-stimulating factor therapy for patients with neutropenia and/or neutrophil dysfunction secondary to glycogen storage disease type 1b

Blood ◽  
2001 ◽  
Vol 97 (2) ◽  
pp. 376-382 ◽  
Author(s):  
Stanley Calderwood ◽  
Laurie Kilpatrick ◽  
Steven D. Douglas ◽  
Melvin Freedman ◽  
Kim Smith-Whitley ◽  
...  
Keyword(s):  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Neutrophil Function ◽  
Glycogen Storage ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Marrow Cellularity ◽  
Neutrophil Dysfunction ◽  
Stimulating Factor

Abstract The purpose of this study was to evaluate the efficacy and toxicity of recombinant human granulocyte colony-stimulating factor (rhG-CSF) therapy in patients with neutropenia and/or neutrophil dysfunction secondary to glycogen storage disease (GSD) type 1b. Thirteen patients with neutropenia and/or neutrophil dysfunction secondary to GSD type 1b were treated with rhG-CSF. The effects of therapy on neutrophil numbers and in vitro neutrophil function and on bone marrow cellularity and morphology were studied. The clinical status of the patients and the occurrence of adverse events associated with rhG-CSF use were monitored. Use of rhG-CSF therapy was associated with a significant increase in circulating neutrophil numbers (P < .01) and an improvement in neutrophil function as assessed in vitro. In addition, rhG-CSF therapy produced a significant increase in marrow cellularity and an increase in myeloid:erythroid (M:E) ratio, indicating stimulation of granulopoeisis. No adverse effects on marrow function were noted; in particular, no myelodysplasia or marrow exhaustion was seen. Use of rhG-CSF therapy was associated with objective and subjective improvements in infection-related morbidity. The therapy was well tolerated, although all patients developed splenomegaly, and 5 patients developed mild hypersplenism that did not require any specific treatment. rhG-CSF therapy is efficacious in the management of neutropenia and neutrophil dysfunction associated with GSD type 1b. Patients on this therapy need to be monitored for hypersplenism. Continued follow-up will be necessary to confirm long-term safety; however, no significant short-term toxicity was noted.

scholarly journals Characterization of influenza A virus activation of the human neutrophil

Blood ◽  
1990 ◽  
Vol 75 (1) ◽  
pp. 218-226 ◽  
Author(s):  
KL Hartshorn ◽  
M Collamer ◽  
MR White ◽  
JH Schwartz ◽  
AI Tauber
Keyword(s):  
Influenza A Virus ◽  
Respiratory Burst ◽  
Influenza A ◽  
Neutrophil Activation ◽  
Kinase C ◽  
Activation Mechanisms ◽  
Neutrophil Dysfunction

Neutrophil dysfunction consequent to influenza A virus infection has been described in vivo and in vitro and may contribute to the serious bacterial sequelae which occur in influenza-infected hosts. On the premise that such dysfunction may represent a form of “deactivation,” we sought to characterize neutrophil activation by the virus in comparison with other agonists. The virus induces a respiratory burst in which H2O2 (but not O2-) are formed. Preceding the respiratory burst, a rise in intracellular calcium (Ca2+i) is noted, but both responses are nearly independent of extracellular Ca2+, unlike those elicited by the other well-characterized Ca2+-dependent agonists, formyl-methyl-leucyl-phenylalanine (FMLP), or Concanavalin-A (Con-A). The Ca2+ increase is paralleled by IP3 generation, implying that it is the result of phospholipase C (PLC) activation. The virus also elicits neutrophil membrane depolarization, which is independently mediated from the Ca2+ increase and respiratory burst and may reflect protein kinase C (PK-C) activation. Virus-induced responses are insensitive to pertussis toxin (PT); cholera toxin does inhibit these responses but in a nonspecific manner. Thus, although influenza virus activates PLC in neutrophils, it does so in a PT-insensitive manner and does not elicit or require a discernible Ca2+ influx to generate a respiratory burst response. In aggregate, the data indicate that influenza A virus activates neutrophils in a manner distinct from that of other well- described neutrophil agonists. These results illustrate the diversity of neutrophil activation mechanisms and support the notion that further characterization of this pathway may facilitate understanding of neutrophil dysfunction induced by the virus.

The Effect of LVAD Pressure Sensitivity on the Assisted Circulation Under Consideration of a Mitral Insufficiency: An In Vitro Study

2018 ◽  
Vol 42 (10) ◽  
pp. E304-E314 ◽  
Author(s):  
Roland Graefe ◽  
Christof Beyel ◽  
Andreas Henseler ◽  
Reiner Körfer ◽  
Ulrich Steinseifer ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Vitro Study ◽  
Assisted Circulation ◽  
Mitral Insufficiency ◽  
Pressure Sensitivity

A Compact Centrifugal Blood Pump for Extracorporeal Circulation: Design and Performance

1987 ◽  
Vol 109 (3) ◽  
pp. 272-278 ◽  
Author(s):  
Shinobu Tanaka ◽  
Shuzo Yamamoto ◽  
Ken-ichi Yamakoshi ◽  
Akira Kamiya
Keyword(s):  
Thrombus Formation ◽  
Animal Experiments ◽  
Left Ventricular ◽  
Blood Pump ◽  
Assisted Circulation ◽  
In Vitro Tests ◽  
Outer Diameter ◽  
Centrifugal Blood Pump ◽  
And Performance

A new compact centrifugal blood pump driven by a miniature DC servomotor has been designed for use for short-term extra corporeal and cardiac-assisted circulation. The impeller of the pump was connected directly to the motor by using a simple-gear coupling. The shaft for the impeller was sealed from blood by both a V-ring and a seal bearing. Either pulsatile or nonpusatile flow was produced by controlling the current supply to the motor. The pump characteristics and the degree of hemolysis were evaluated with regard to the configuration of the impeller with a 38-mm outer diameter in vitro tests; the impeller having the blade angles at the inlet of 20 deg and at the outlet of 50 deg was the most appropriate as a blood pump. The performance in an operation, hemolysis and thrombus formation in the pump were assessed by a left ventricular bypass experiment in dogs. It was suggested by this study that this prototype pump appears promising for use not only in animal experiments but also in clinical application.

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