Alterations in L-selectin expression and elastase activity in neutrophils from patients receiving granulocyte colony-stimulating factor alone or in conjunction with high-dose chemotherapy with autologous bone marrow transplantation.
We determined L-selectin expression and elastase levels in neutrophils obtained from patients receiving granulocyte colony-stimulating factor (G-CSF) either alone (given for increasing peripheral progenitor cells for harvest) or in combination with high-dose chemotherapy with autologous bone transplantation support (BMT). Administration of G-CSF alone for 3-5 days produced a decrease in L-selectin expression in neutrophils (25 +/- 4 versus 7 +/- 1, mean +/- SEM; mean channel fluorescence, n = 10) with no effect on neutrophil elastase activity (3.1 +/- 0.3 versus 3.4 +/- 0.6; micrograms elastase/million cells; n = 9). In contrast, in patients in the BMT group the L-selectin expression was increased (26 +/- 2 versus 38 +/- 3; n = 20) and elastase activity was markedly decreased (2.9 +/- 0.2 versus 1.4 +/- 0.2, n = 12) compared with values before BMT. The changes in L-selectin expression correlated with the ability of neutrophils to adhere to human umbilical vein endothelial cells. The decrease in the neutrophil elastase activity was not associated with an increase in the plasma elastase/alpha 1-antitrypsin complex levels, indicating that the decrease in the neutrophil elastase activity is not caused by activation of neutrophils and release of the enzyme into the plasma. Administration of G-CSF alone did not cause a decrease in the neutrophil elastase activity but increased plasma elastase/alpha 1-antitrypsin complex levels. There was no change in CR3 expression on neutrophils under any of these conditions. These observations suggest that the changes seen in neutrophils during BMT are influenced by various factors associated with BMT other than the administered cytokine alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Rao
K M
KM
Department of Veterans Affairs Medical Center, Durham, North Carolina.
Currie
M S
MS
Cohen
H J
HJ
Peters
W P
WP
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D001943:Breast Neoplasms / Q000097:blood / Q000628:therapy; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000097:blood*; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D019041:L-Selectin; D019272:Leukocyte Elastase / Q000097:blood*; D016177:Macrophage-1 Antigen / Q000097:blood; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010196:Pancreatic Elastase / Q000097:blood*; D014182:Transplantation, Autologous
D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D016177:Macrophage-1 Antigen; D019041:L-Selectin; D016179:Granulocyte Colony-Stimulating Factor; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase