Changes in actin state and chemotactic peptide receptor expression in granulocytes during cytokine administration after autologous bone marrow transplantation.
We studied the changes in actin state and chemotactic peptide receptor expression in granulocytes from patients receiving different cytokines following high dose chemotherapy and autologous bone marrow transplantation (ABMT). The F-actin content in granulocytes was higher in all patients following ABMT. However, in patients receiving granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF) the increase in F-actin content was much greater than in those not receiving these cytokines (159, 149, and 90% for G-CSF, M-CSF, and noncytokine group, respectively). Patients receiving granulocyte-macrophage colony-stimulating factor (GM-CSF) had only a 62% increase in the F-actin content, which was not statistically significant from patients undergoing ABMT without any cytokines. Although the basal level of F-actin was high following ABMT, granulocytes from all patients showed an additional increase in F-actin content after stimulation with either the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) or phorbol myristate acetate (PMA). The chemotactic peptide receptor expression was significantly higher in patients treated with ABMT alone or ABMT plus G-CSF. These observations suggest that the granulocytes generated following ABMT and cytokine administration may have different functional potential depending on the cytokine administered. Further studies to evaluate these potential differences are essential to devise optimal therapeutic protocols for maximizing the granulocyte protective function in this clinical setting.
Rao
K M
KM
Geriatric Research, Education and Clinical Center, VA Medical Center, Durham, NC.
Kilby
D L
DL
Currie
M S
MS
Cohen
H J
HJ
Peters
W P
WP
D000199:Actins / Q000097:blood*; D016026:Bone Marrow Transplantation; D016207:Cytokines / Q000494:pharmacology*; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000199:Actins; D016207:Cytokines; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D016179:Granulocyte Colony-Stimulating Factor; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate