In vitro and in vivo effects of granulocyte colony-stimulating factor on neutrophils in glycogen storage disease type 1B: granulocyte colony-stimulating factor therapy corrects the neutropenia and the defects in respiratory burst activity and Ca2+ mobilization
| Autor: | L J, McCawley, H M, Korchak, S D, Douglas, D E, Campbell, P S, Thornton, C A, Stanley, L, Baker, L, Kilpatrick |
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| Rok vydání: | 1994 |
| Předmět: |
Adult
Male Neutropenia Adolescent Neutrophils Granulocyte-Macrophage Colony-Stimulating Factor Macrophage-1 Antigen Glycogen Storage Disease Type I In Vitro Techniques Monocytes N-Formylmethionine Leucyl-Phenylalanine Chemotaxis Leukocyte Child Preschool Granulocyte Colony-Stimulating Factor Humans Calcium Female Child Respiratory Burst |
| Zdroj: | Pediatric research. 35(1) |
| ISSN: | 0031-3998 |
| Popis: | Children with glycogen storage disease (GSD) type 1b are susceptible to recurrent bacterial infections and have chronic neutropenia accompanied by phagocytic cell dysfunction including decreased superoxide anion (O2-) generation, calcium (Ca2+) mobilization, and chemotactic activity. Granulocyte colony-stimulating factor (G-CSF), a cytokine that corrects neutropenia in other diseases, in vitro enhances f-Met-Leu-Phe-triggered neutrophil O2- generation. Short-term pretreatment (15 min) of GSD 1b neutrophils with G-CSF increased the rate of O2- production (p0.01); however, this rate was still significantly below the rate of O2- production in control neutrophils. Recombinant human G-CSF (5 micrograms/kg/d) was administered s.c. to a GSD 1b patient. Before treatment, absolute neutrophil counts were500/mm3. Two d after G-CSF administration, the absolute neutrophil counts increased to 1333 and remained in the normal range during a 12-mo follow-up period. In vivo, G-CSF therapy increased f-Met-Leu-Phe-stimulated O2- production to 52% of control after 1 mo, and by mo 4, O2- production reached control levels. Our previous studies (J Clin Invest 56:196-202, 1990) demonstrated that decreased O2- production in neutrophils was associated with impaired Ca2+ mobilization. In vivo administration of G-CSF increased f-Met-Leu-Phe-triggered Ca2+ mobilization by neutrophils to 43% of control by mo 1 of G-CSF therapy and to 93% of control by mo 4, thus paralleling the improvements in O2- generation. In contrast, G-CSF therapy had no effect on the defective neutrophil chemotaxis. In summary, G-CSF therapy produced a rapid increase in circulating neutrophils and a gradual correction of O2- production.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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