title: 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.
abstract: 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 (p < 0.01); 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 were < 500/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)
authors.affiliation: Department of Pediatrics, University of Pennsylvania School of Medicine, Children's Hospital of Philadelphia, Joseph Stokes Jr. Research Institute 19104.
authors.forename: L J
authors.initials: LJ
authors.lastname: McCawley
authors.forename: H M
authors.initials: HM
authors.lastname: Korchak
authors.forename: S D
authors.initials: SD
authors.lastname: Douglas
authors.forename: D E
authors.initials: DE
authors.lastname: Campbell
authors.forename: P S
authors.initials: PS
authors.lastname: Thornton
authors.forename: C A
authors.initials: CA
authors.lastname: Stanley
authors.forename: L
authors.initials: L
authors.lastname: Baker
authors.forename: L
authors.initials: L
authors.lastname: Kilpatrick
mesh_terms: D000293:Adolescent; D000328:Adult; D002118:Calcium / Q000097:blood; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D005953:Glycogen Storage Disease Type I / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009503:Neutropenia / Q000188:drug therapy; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects
chemical_list: D016177:Macrophage-1 Antigen; D016179:Granulocyte Colony-Stimulating Factor; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002118:Calcium