Chronic Neutropenia and Defect in Superoxide Generation of Granulocytes in Two Patients: Enhancement of Bactericidal Capacity and Respiratory Burst Activity by Treatment with Recombinant Human Granulocyte Colony-Stimulating Factor

Káposzta, Rita; Maródi, László

doi:10.1203/00006450-199501000-00011

Cited by 10 publications

(5 citation statements)

References 2 publications

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“…The most evident effect of G-CSF pretreatment is the significant increase in both the number of peripheral neutrophils and their phagocytic activity. This increase presumably leads to improved control of the infection in the systemic compartment by reducing the number of bacteria (1,4,6,12,13,19,21,22,24,26), as also seen in the present study. In pneumococcal meningitis, approximately 70% of patients become bacteremic, and bacteremia has been associated with an increased risk of mortality (5, 10, 11, 25; D. van de Beek and J. de Gans, Abstr.…”

Section: Discussionsupporting

confidence: 71%

Attenuation of the Bacterial Load in Blood by Pretreatment with Granulocyte-Colony-Stimulating Factor Protects Rats from Fatal Outcome and Brain Damage duringStreptococcus pneumoniaeMeningitis

Brandt

Lundgren²,

Lund

et al. 2004

Infect Immun

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A model of pneumococcal meningitis in young adult rats receiving antibiotics once the infection was established was developed. The intent was to mimic clinical and histopathological features of pneumococcal meningitis in humans. The primary aim of the present study was to evaluate whether medical boosting of the peripheral neutrophil count affected the outcome of the meningitis. The risk of terminal illness over the first 7 days after infection was significantly reduced for rats who had elevated peripheral white blood cell counts after receiving granulocyte-colony-stimulating factor (G-CSF) prior to the infection compared to that for untreated rats (P ‫؍‬ 0.039 by the log rank test). The improved outcome was associated with reduced signs of cerebral cortical damage (P ‫؍‬ 0.008). Furthermore, the beneficial effects of G-CSF were associated with reduced bacterial loads in the cerebrospinal fluid (median, 1.1 ؋ 10 5 versus 2.9 ؋ 10 5 CFU/ml; P ‫؍‬ 0.023) and in blood (median, 2.9 ؋ 10 2 versus 6.3 ؋ 10 2 CFU/ml; P ‫؍‬ 0.024), as well as attenuated pleocytosis (median, 800 ؋ 10 6 versus 1,231 ؋ 10 6 cells/liter; P ‫؍‬ 0.025), 24 h after the infection. Conversely, initiation of G-CSF therapy 28 h postinfection did not alter the clinical or histological outcome relative to that for non-G-CSFtreated rats. The magnitude of bacteremia and pretreatment with G-CSF were found to be prognostic factors for both outcome and brain damage. In summary, elevated neutrophil levels prior to the development of meningitis result in reduced risks of death and brain damage. This beneficial effect is most likely achieved through improved control of the systemic disease.

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Section: Discussionsupporting

confidence: 71%

Attenuation of the Bacterial Load in Blood by Pretreatment with Granulocyte-Colony-Stimulating Factor Protects Rats from Fatal Outcome and Brain Damage duringStreptococcus pneumoniaeMeningitis

Brandt

Lundgren²,

Lund

et al. 2004

Infect Immun

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“…G‐CSF is a lineage‐specific haematopoietic cytokine widely used to combat the risk of infections resulting from both congenital and acquired neutropenias (Lindemann et al , 1989; Negrin et al , 1989; Elsner et al , 1993; Kaposzta & Marodi, 1995). G‐CSF stimulates the proliferation and differentiation of haemopoietic progenitor cells of neutrophilic granulocytes (Demetri & Griffin, 1991; Schwinger et al , 1993).…”

Section: Discussionmentioning

confidence: 99%

Subcellular localization and mobilization of carcinoembryonic antigen‐related cell adhesion molecule 8 in human neutrophils

Zhao¹,

Furebring

Xu³

2004

Br J Haematol

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Summary The subcellular localization and mobilization of carcinoembryonic antigen‐related cell adhesion molecule 8 (CEACAM8) was investigated quantitatively in human neutrophils. In resting neutrophils the majority of CEACAM8 was present in the secondary granules, and a small amount of CEACAM8 was present in a light membrane fraction. Stimulation of the neutrophils with phorbol 12‐myristate 13‐acetate caused a dramatic increase in the content of CEACAM8 in the light membrane fraction, suggesting a translocation of CEACAM8 to the plasma membrane from intracellular pools. The cellular content of CEACAM8 in the neutrophils was estimated to be 82·4 ± 8·9 ng/106 cells (mean ± SE, n = 10). Administration of granulocyte colony‐stimulating factor (G‐CSF) to healthy individuals resulted in an increased content of CEACAM8 in neutrophils on day 1, which decreased on day 4. However, the content of CEACAM8 in the light membrane fraction was increased on day 4, possibly due to the stimulation by induced secondary cytokines, such as tumour necrosis factor‐α (TNF‐α). This study establishes the secondary granules as the major intracellular pools of CEACAM8 in human neutrophils, from which it may translocate to the plasma membranes upon stimulation of the cells. The translocation of CEACAM8 seen in vivo after G‐CSF administration is probably indirect and caused by cytokines such as TNF‐α.

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“…This cytokine induces the maturation and proliferation of mature myeloid cells 25 and induces a novel population of neutrophils with altered biochemical, 26,27 functional, 20,28-32 and survival 33,34 characteristics. However, although the clinical benefits of G-CSF are well described, [35][36][37][38][39] the efficacy of granulocytes mobilized by G-CSF and their capacity for storage have not been directly investigated.…”

Section: Discussionmentioning

confidence: 99%

Functional characteristics of neutrophils collected and stored after administration of G–CSF

2000

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Chronic Neutropenia and Defect in Superoxide Generation of Granulocytes in Two Patients: Enhancement of Bactericidal Capacity and Respiratory Burst Activity by Treatment with Recombinant Human Granulocyte Colony-Stimulating Factor

Cited by 10 publications

References 2 publications

Attenuation of the Bacterial Load in Blood by Pretreatment with Granulocyte-Colony-Stimulating Factor Protects Rats from Fatal Outcome and Brain Damage duringStreptococcus pneumoniaeMeningitis

Attenuation of the Bacterial Load in Blood by Pretreatment with Granulocyte-Colony-Stimulating Factor Protects Rats from Fatal Outcome and Brain Damage duringStreptococcus pneumoniaeMeningitis

Subcellular localization and mobilization of carcinoembryonic antigen‐related cell adhesion molecule 8 in human neutrophils

Functional characteristics of neutrophils collected and stored after administration of G–CSF

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