title: Neutrophil defense in patients undergoing bone marrow transplantation: bactericidal/permeability-increasing protein (BPI) and defensins in graft-derived neutrophils.
abstract: BACKGROUND
  Even after neutrophil counts return to near normal levels, patients undergoing myeloablative chemotherapy and bone marrow transplantation (BMT) are at risk for invasive bacterial infections, raising the possibility that their neutrophil function might be impaired. To assess potential qualitative defects in neutrophil function in patients undergoing BMT, we measured neutrophil content of the antimicrobial (poly)peptides BPI and defensins.
  
  
  METHODS
  Neutrophil extracts were analyzed for content of BPI by Western blotting and ELISA and for defensin peptides by acid-urea polyacrylamide gel electrophoresis (PAGE). Antibacterial activity of neutrophil extracts was measured against Escherichia coli K1/r, a clinical isolate sensitive to synergistic killing by BPI and defensins.
  
  
  RESULTS
  Neutrophil extract BPI content on post-BMT days +20, +30, and +100 (169+/-35, 232+/-57, and 160+/-55 ng per 106 neutrophils, respectively) was similar to the neutrophil BPI content of normal controls (163+/-35 ng per 106 neutrophils). Neutrophil defensin content also did not vary during this time-span. Activity of neutrophil extracts against E. coli K1/r did not differ between BMT patients and controls.
  
  
  CONCLUSIONS
  At post-BMT days +20 to +100, neutrophils derived from engrafted marrow contain normal quantities of BPI and defensins. Any deficiencies of neutrophil function during this phase are not due to inadequate expression of these antimicrobial (poly)peptides but could reflect abnormalities in other aspects of neutrophil function.
authors.affiliation: Division of Infectious Diseases, General Clinical Research Center, and Medicine, Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Ofer
authors.initials: O
authors.lastname: Levy
authors.forename: Richard B
authors.initials: RB
authors.lastname: Sisson
authors.forename: Hamilton E
authors.initials: HE
authors.lastname: Fryer
authors.forename: Donald
authors.initials: D
authors.lastname: Goldmann
authors.forename: Erika
authors.initials: E
authors.lastname: Valore
authors.forename: Tomas
authors.initials: T
authors.lastname: Ganz
authors.forename: Mark L
authors.initials: ML
authors.lastname: White
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Carroll
authors.forename: Leslie
authors.initials: L
authors.lastname: Lehmann
authors.forename: Eva C
authors.initials: EC
authors.lastname: Guinan
mesh_terms: D000293:Adolescent; D000328:Adult; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation; D002457:Cell Extracts / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D023082:Defensins / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000187:drug effects; D006801:Humans; D007223:Infant; D008565:Membrane Proteins; D009504:Neutrophils / Q000737:chemistry / Q000502:physiology*; D012016:Reference Values
chemical_list: D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002457:Cell Extracts; D023082:Defensins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; C021623:bactericidal permeability increasing protein