The In Vitro Effects of Granulocyte and Granulocyte-Macrophage Colony-Stimulating Factor on Interleukin-3-Dependent Proliferation of Human Neonatal Circulating Progenitor Cells

Russell, Alison; Davies, E. G.; Gibson, Frances M.; Gordon‐Smith, E. C.

doi:10.1203/00006450-199505000-00013

Cited by 7 publications

(4 citation statements)

References 14 publications

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“…Additionally, it is likely that even segmented cells are not fully mature, as their expression of key markers such as CD16 is much lower than isolated circulating neutrophils. This is not for a lack of G-CSF receptor signalling, as the concentrations of G-CSF used in culture exceed normal endogenous circulating concentrations of 100-1000 pg/mL 23 , but rather may be due to the lack of mechanical and cellular components of the bone marrow microenvironment, or other complementary cytokines such as IL-6, IL-3, and GM-CSF. The exclusion of other cytokines in this method aids the generation of a highly pure population of neutrophils, as the inclusion of other cytokines may lead to non-neutrophil lineage commitment 24 .…”

Section: Discussionmentioning

confidence: 99%

Efficient Methods for Target Gene Manipulation in Haematopoietic Stem Cell Derived Human Neutrophils

Fox

Brelstaff

et al. 2023

Preprint

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Neutrophils are the most abundant leukocyte in humans and the principal effectors of the innate immue response. Genetic modification of human neutrophils is challenging due to their short lifespan and tendency to activate in response to even minor perturbation. However, genetic manipulation of haematopoietic progenitor cells and subsequent directed differentation into neutrophils represents a potential avenue to study the contributions of individual genes and pathways to human neutrophil function. Here we present a method of directed granulocytic CD34+ progenitor differentiation into neutrophils capable of key functions such as priming and neutrophil extracellular trap (NET) formation. We further show that differentiating progenitors can be efficiently and stably modified by lentiviral gene delivery and Cas9-gRNP nucleofection to produce potent and activation-free gene knockdown in mature neutrophils, thereby providing new tools for understanding the contribution of neutrophils to health and disease. Using this model we have shown that, contrary to previous reports, CD11b is not required for phagocytosis of serum-opsonised bacterial particles.

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Section: Discussionmentioning

confidence: 99%

Efficient Methods for Target Gene Manipulation in Haematopoietic Stem Cell Derived Human Neutrophils

Fox

Brelstaff

et al. 2023

Preprint

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“…55 In vitro functional experiments have confirmed that GM-CSF can prime term and preterm neonate neutrophils for enhanced chemotactic and respiratory burst responses to appropriate stimuli 2560 61Similarly, granulocyte and granulocyte-macrophage committed progenitors isolated from neonate blood samples respond well to the proliferative stimuli of exogenous G- and GM-CSF, respectively, in vitro 62. In our laboratory, progenitors from preterm neonates (median gestation 31 weeks) were at least as responsive to GM-CSF as those from adults 63.…”

Section: Colony Stimulating Factor Physiology In Neonatesmentioning

confidence: 95%

Haemopoietic colony stimulating factors for preterm neonates

Carr

Modi

1997

Archives of Disease in Childhood - Fetal and Neonatal Edition

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“…RhG-CSF mobilises stem cells and stimulates the proliferation and differentiation of neonatal progenitor cells into mature neutrophils [5], and enhances neutrophil function [6]. In neonatal rats rhG-CSF given either prophylactically or as treatment has been shown to improve survival from group B streptococci [6].…”

Section: Rbg-csf and Rhgm-csfmentioning

confidence: 99%

New modalities for treating neonatal infection

Bedford-Russell

1996

Eur J Pediatr

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While the overall incidence of infection has remained constant at approximately 7/1000 livebirths, the last decade has witnessed a reduction in early onset infections and a relative increase in nosocomial sepsis, chiefly with coagulase-negative staphylococci. Immaturity of host defence mechanisms contributes to an increasing susceptibility to infection with decreasing gestational age and birth weight. In the past, efforts to enhance host defence have included the use of granulocyte infusions, fresh frozen plasma, exchange blood transfusions and immunoglobulin therapy. Current trials are investigating the use of agents which enhance endogenous defence mechanisms, such as, recombinant human granulocyte colony-stimulating factant and recombinant human granulocyte-macrophage colony-stimulating factor and of pentoxifylline. In the meantime strict attention to handwashing and aseptic technique remain the best methods of preventing nosocomial sepsis.

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The In Vitro Effects of Granulocyte and Granulocyte-Macrophage Colony-Stimulating Factor on Interleukin-3-Dependent Proliferation of Human Neonatal Circulating Progenitor Cells

Cited by 7 publications

References 14 publications

Efficient Methods for Target Gene Manipulation in Haematopoietic Stem Cell Derived Human Neutrophils

Efficient Methods for Target Gene Manipulation in Haematopoietic Stem Cell Derived Human Neutrophils

Haemopoietic colony stimulating factors for preterm neonates

New modalities for treating neonatal infection

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