Effect of recombinant bovine granulocyte colony-stimulating factor covalently bound to polyethylene glycol injection on neutrophil number and function in periparturient dairy cows

Abstract We postulated that defective generation of granulocyte colony- stimulating factor (G-CSF) by cells of newborn infants might underlie their deficiencies in upregulating neutrophil production and function during bacterial infection. To test this, we isolated monocytes from the blood of preterm neonates, term neonates, and adults and, after stimulation with various concentrations of interleukin-1 alpha (IL-1 alpha) or lipopolysaccharide (LPS), quantified G-CSF concentrations in cell supernatants and G-CSF mRNA in cell lysates. When stimulated with plateau concentrations of IL-1 alpha for 24 hours, G-CSF concentrations were higher in supernatants of adult cells (8,699 +/- 5,529 pg/10(6) monocytes) than in those from term infants (2,557 +/- 442 pg, P < .05) or from preterm infants (879 +/- 348 pg, P < .05 v adults). When stimulated with plateau concentrations of LPS, supernatants of monocytes from preterm neonates had less G-CSF than did those from term neonates or adults. G-CSF mRNA content was low in cells from preterm infants, higher in those from term infants, and highest in those from adults. On the basis of the in vitro studies, we speculated that serum G-CSF concentrations might be less elevated in neutropenic neonates than in neutropenic adults. Indeed, serum concentrations were relatively low in all nonneutropenic subjects; 92 +/- 34 pg/mL (mean +/- SEM) in 10 preterm neonates, 114 +/- 21 pg/mL in 16 term neonates, and 45 +/- 13 pg/mL in 11 healthy adults. Serum concentrations were not elevated in 7 neutropenic neonates (39 +/- 17 pg/mL) but were in 8 neutropenic adults (2101 +/- 942 pg/mL, P < .05 v healthy adults). Other studies suggested that the lower G-CSF production in neonates is not counterbalanced by a heightened sensitivity of G-CSF--responsive progenitors to G-CSF. Therefore, we speculate that newborn infants, particularly those delivered prematurely, generate comparatively low quantities of G-CSF after inflammatory stimulation, and that this might constitute part of the explanation for their defective upregulation of neutrophil production and function during infection.

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Recombinant granulocyte colony-stimulating factor administration to healthy volunteers: induction of immunophenotypically and functionally altered neutrophils via an effect on myeloid progenitor cells

Blood ◽

10.1182/blood.v82.11.3265.3265 ◽

1993 ◽

Vol 82 (11) ◽

pp. 3265-3272 ◽

Cited By ~ 112

Author(s):

JM Kerst ◽

M de Haas ◽

CE van der Schoot ◽

IC Slaper-Cortenbach ◽

M Kleijer ◽

...

Keyword(s):

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Myeloid Progenitor ◽

Leukocyte Alkaline Phosphatase ◽

Subcutaneous Dose ◽

Myeloid Progenitor Cells ◽

Membrane Bound ◽

And Function ◽

Stimulating Factor

Abstract We performed a detailed kinetic study on the in vivo effect of a single subcutaneous dose of granulocyte colony-stimulating factor (G-CSF; 300 micrograms) in four healthy individuals on the expression and function of neutrophil Fc gamma receptors (Fc gamma R). G-CSF did not induce Fc gamma RI (CD64) on circulating neutrophils. However, neutrophils newly formed in response to G-CSF were Fc gamma RI positive and were able to perform antibody-dependent cellular cytotoxicity in an Fc gamma RI- dependent way. Fc gamma RII (CD32) expression was not changed significantly. Fc gamma RIII (CD16, phosphatidylinositol-linked) expression, slightly increased immediately (30 minutes) postinjection, was found to be strongly decreased on the newly formed population. For comparison, we studied the expression of the PI-linked proteins leukocyte alkaline phosphatase (LAP) and CD14. Intracellular levels of LAP mirrored the biphasic expression pattern as membrane-bound Fc gamma RIII. In contrast, CD14 expression on neutrophils was initially constant, followed by high levels on the newly formed neutrophils. Soluble CD14 levels were found to be elevated transiently, whereas peak levels of soluble Fc gamma III were observed as late as 6 days postinjection. In conclusion, we have shown that G-CSF results in an immunophenotypically and functionally altered neutrophil population for an important part as a result of its effect on myeloid precursor cells.

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Granulocyte colony‐stimulating factor treatment in chronic Chagas disease: preservation and improvement of cardiac structure and function

The FASEB Journal ◽

10.1096/fj.09-137869 ◽

2009 ◽

Vol 23 (11) ◽

pp. 3843-3850 ◽

Cited By ~ 18

Author(s):

Simone G. Macambira ◽

Juliana F. Vasconcelos ◽

Claudio R. S. Costa ◽

Wilfried Klein ◽

Ricardo S. Lima ◽

...

Keyword(s):

Chagas Disease ◽

Structure And Function ◽

Cardiac Structure ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Cardiac Structure And Function ◽

And Function ◽

Chronic Chagas Disease ◽

Stimulating Factor

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Long-acting Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF) with a Trimer-Structured Polyethylene Glycol

Journal of Pharmaceutical Investigation ◽

10.4333/kps.2010.40.6.379 ◽

2010 ◽

Vol 40 (6) ◽

pp. 379-386 ◽

Cited By ~ 1

Keyword(s):

Polyethylene Glycol ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Long Acting ◽

Stimulating Factor

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Production of granulocyte colony-stimulating factor in vitro by monocytes from preterm and term neonates [see comments]

Blood ◽

10.1182/blood.v82.8.2478.bloodjournal8282478 ◽

1993 ◽

Vol 82 (8) ◽

pp. 2478-2484 ◽

Cited By ~ 1

Author(s):

KR Schibler ◽

KW Liechty ◽

WL White ◽

RD Christensen

Keyword(s):

Newborn Infants ◽

Preterm Neonates ◽

Granulocyte Colony Stimulating Factor ◽

Serum Concentrations ◽

Colony Stimulating Factor ◽

Term Infants ◽

Term Neonates ◽

And Function ◽

Stimulating Factor

We postulated that defective generation of granulocyte colony- stimulating factor (G-CSF) by cells of newborn infants might underlie their deficiencies in upregulating neutrophil production and function during bacterial infection. To test this, we isolated monocytes from the blood of preterm neonates, term neonates, and adults and, after stimulation with various concentrations of interleukin-1 alpha (IL-1 alpha) or lipopolysaccharide (LPS), quantified G-CSF concentrations in cell supernatants and G-CSF mRNA in cell lysates. When stimulated with plateau concentrations of IL-1 alpha for 24 hours, G-CSF concentrations were higher in supernatants of adult cells (8,699 +/- 5,529 pg/10(6) monocytes) than in those from term infants (2,557 +/- 442 pg, P < .05) or from preterm infants (879 +/- 348 pg, P < .05 v adults). When stimulated with plateau concentrations of LPS, supernatants of monocytes from preterm neonates had less G-CSF than did those from term neonates or adults. G-CSF mRNA content was low in cells from preterm infants, higher in those from term infants, and highest in those from adults. On the basis of the in vitro studies, we speculated that serum G-CSF concentrations might be less elevated in neutropenic neonates than in neutropenic adults. Indeed, serum concentrations were relatively low in all nonneutropenic subjects; 92 +/- 34 pg/mL (mean +/- SEM) in 10 preterm neonates, 114 +/- 21 pg/mL in 16 term neonates, and 45 +/- 13 pg/mL in 11 healthy adults. Serum concentrations were not elevated in 7 neutropenic neonates (39 +/- 17 pg/mL) but were in 8 neutropenic adults (2101 +/- 942 pg/mL, P < .05 v healthy adults). Other studies suggested that the lower G-CSF production in neonates is not counterbalanced by a heightened sensitivity of G-CSF--responsive progenitors to G-CSF. Therefore, we speculate that newborn infants, particularly those delivered prematurely, generate comparatively low quantities of G-CSF after inflammatory stimulation, and that this might constitute part of the explanation for their defective upregulation of neutrophil production and function during infection.

Download Full-text