Neutrophil migration is defective during recombinant human granulocyte-macrophage colony-stimulating factor infusion after autologous bone marrow transplantation in humans.
We have previously reported that continuous intravenous (IV) administration of recombinant granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) to humans following high-dose alkylating agent chemotherapy and autologous bone marrow support (ABMS) results in myeloid bone marrow maturation, accelerated granulocyte recovery, and reduced treatment-related toxicity. However, we found that leukocyte counts declined rapidly after discontinuation of rHuGM-CSF therapy, which suggests possible growth factor effects on leukocyte margination and migration. For these reasons we studied granulocyte margination by using 111In-labeled autologous granulocytes and found similar granulocyte margination before (21.5% +/- 13.4%) and during continuous IV rHuGM-CSF infusion (23.3% +/- 9.6%). Phagocytosis of Cryptococcus neoformans and granulocyte hydrogen peroxide production was similar before and during rHuGM-CSF infusion and similar to patients treated with the same high-dose chemotherapy and ABMS but not receiving growth factor. However, migration of granulocytes to a sterile inflammatory site was markedly reduced during continuous rHuGM-CSF infusion (1.2 +/- 0.9 WBCs/cm2, 24 hr) as compared with baseline (39.6 +/- 17.7 WBCs/cm2/24 hr; P less than .0008). These findings may be of relevance when extravascular granulocytes are required for host defense.
D016026:Bone Marrow Transplantation; D002465:Cell Movement / Q000187:drug effects*; D003115:Colony-Stimulating Factors / Q000008:administration & dosage*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006098:Granulocytes / Q000187:drug effects / Q000473:pathology; D006133:Growth Substances / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology*; D010101:Oxygen Consumption / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage*; D014182:Transplantation, Autologous
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor