Mobilization of granules in neutrophils from patients with myeloproliferative disorders.
Neutrophil granule subsets and dynamics were studied in 4 patients with polycythemia vera/myelofibrosis and 2 patients with chronic myelogenous leukemia. Alkaline phosphatase, a marker for the membrane of secretory vesicles (the most readily mobilizable pool of intracellular membranes in neutrophils) was highly elevated in the PV/MF patients and significantly reduced in the CML patients. In spite of this, the amount of secretory vesicles was normal as judged by the content of albumin, and of the membrane protein cytochrome b-245 and CD11b, both partially localized in secretory vesicles. Gelatinase granules were present in all patients. The azurophil granules were lighter than normal in both CML patients. SDS-PAGE protein profiles indicated absence of defensins from azurophil granules from 1 CML patient. In addition, a 41-42 kD doublet protein band was absent from 2 PV and 1 CML patient, and reduced in the other CML patient. No difference in mobilization of granules was observed between patient neutrophils and control neutrophils. Also, stimulation with 10(-8) mol/l N-formyl-methionyl-leucyl-phenylalanine induced normal increases in intracellular Ca2+ in patient neutrophils. These results indicate that stimulus-response coupling leading to granule exocytosis is intact in neutrophils from patients with myeloproliferative disorders.
Department of Hematology L, Rigshospitalet, Copenhagen, Denmark.
N
N
Borregaard
L
L
Kjeldsen
H
H
Sengeløv
D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D002458:Cell Fractionation; D002499:Centrifugation, Density Gradient; D003594:Cytoplasmic Granules / Q000502:physiology*; D010450:Endopeptidases / Q000097:blood; D005260:Female; D018093:Gelatinases; D006801:Humans; D007781:Lactoferrin / Q000097:blood; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000097:blood*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000648:ultrastructure*; D011087:Polycythemia Vera / Q000097:blood; D055728:Primary Myelofibrosis / Q000097:blood; D014155:Transcobalamins / Q000032:analysis
D014155:Transcobalamins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000469:Alkaline Phosphatase; D010450:Endopeptidases; D007781:Lactoferrin; D018093:Gelatinases