title: 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.
abstract: We have identified two unrelated girls with chronic neutropenia [absolute neutrophil counts (ANC) 10-870 and 10-940/microL in patients 1 and 2, respectively] and severe defect in superoxide anion generation by granulocytes. Formyl-methionyl-leucyl-phenylalanine-induced superoxide release was 1.2 +/- 0.9 and 1.9 +/- 1.9% (mean +/- SEM, n = 3) of normal controls', mean value in patients 1 and 2, respectively. However, granulocytes from both patients released a normal amount of superoxide upon stimulation with phorbol myristate acetate. Patient 2 exhibited characteristic features of Duane syndrome, a rare disorder of eye movement. Treatment of the patients with recombinant granulocyte colony-stimulating factor led to significant clinical improvements and reduction of infectious complications and to increases in the ANC, to 400-2100/microL in patient 1 and to 500-3000/microL in patient 2. Treatment with 5 micrograms/kg/d resulted in increased intracellular killing of opsonized Staphylococcus aureus by granulocytes and an enhancement of superoxide release upon stimulation with formyl-methionyl-leucyl-phenylalanine in both patients up to 11.1 +/- 6.0 and 13.5 +/- 7.0% (mean +/- SEM, n = 5) of normal controls', mean value in patient 1 and patient 2, respectively. These data suggested that recombinant human granulocyte colony-stimulating factor treatment enhanced resistance to bacterial infection by stimulation of superoxide generation and increasing the bactericidal capacity of peripheral blood granulocytes.
authors.affiliation: Department of Pediatrics, University School of Medicine, Debrecen, Hungary.
authors.forename: R
authors.initials: R
authors.lastname: Káposzta
authors.forename: L
authors.initials: L
authors.lastname: Maródi
mesh_terms: D001770:Blood Bactericidal Activity / Q000187:drug effects; D002648:Child; D003114:Colony-Forming Units Assay; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006098:Granulocytes / Q000187:drug effects* / Q000378:metabolism; D006105:Granulomatous Disease, Chronic / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009503:Neutropenia / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects; D011994:Recombinant Proteins / Q000627:therapeutic use; D016897:Respiratory Burst / Q000187:drug effects; D013211:Staphylococcus aureus / Q000276:immunology; D013481:Superoxides / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; D013481:Superoxides; D016179:Granulocyte Colony-Stimulating Factor; D009240:N-Formylmethionine Leucyl-Phenylalanine