Neutrophil defense in patients undergoing bone marrow transplantation: bactericidal/permeability-increasing protein (BPI) and defensins in graft-derived neutrophils.
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.
Levy
Ofer
O
Division of Infectious Diseases, General Clinical Research Center, and Medicine, Children's Hospital, Boston, Massachusetts, USA.
Sisson
Richard B
RB
Fryer
Hamilton E
HE
Goldmann
Donald
D
Valore
Erika
E
Ganz
Tomas
T
White
Mark L
ML
Carroll
Stephen F
SF
Lehmann
Leslie
L
Guinan
Eva C
EC
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
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002457:Cell Extracts; D023082:Defensins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; C021623:bactericidal permeability increasing protein