This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ulich, T. R. Articles by Andresen, J. Search for Related Content PubMed PubMed Citation Articles by Ulich, T. R. Articles by Andresen, J.

American Journal of Pathology, Vol 137, 369-376, Copyright © 1990 by American Society for Investigative Pathology

REGULAR ARTICLES

Hematologic effects of recombinant murine granulocyte-macrophage colony- stimulating factor on the peripheral blood and bone marrow

TR Ulich, J del Castillo, I McNiece, L Watson, SM Yin and J Andresen
Department of Pathology, School of Medicine, University of California, Irvine 92717.

Recombinant murine granulocyte-macrophage colony-stimulating factor (GM- CSF) was noted to support rat bone marrow colony formation in vitro. The in vivo hematologic effects of a single intravenous injection of murine GM-CSF were therefore investigated. Doses of murine GM-CSF between 0.1 and 5 micrograms/rat caused an increasing leukocytosis that did not further increase with a dose of 25 micrograms/rat. In contrast, human GM-CSF at 25 micrograms/rat did not induce any significant peripheral hematologic effects. Murine GM-CSF induced peripheral neutrophilia and monocytosis, peaking between 4 and 8 hours and subsiding to baseline by 12 hours. Neutropenia and monocytopenia, which reached a nadir at 15 minutes, preceded the leukocytosis, suggesting that GM-CSF activates these leukocytes and causes transient intravascular margination. A mild lymphopenia occurred between 2 to 8 hours. The bone marrow at 6 hours after injection of GM-CSF demonstrated a variable and slight left-shifted myeloid hyperplasia most noticeable at the level of promyelocytes and myelocytes, suggesting a myeloproliferative effect. The marrow at 6 hours also demonstrated a decrease in mature neutrophils, documenting that the marrow contributes to the increased number of circulating neutrophils. Once-daily injection of GM-CSF for 7 days induced a repetitive daily neutrophilia of the same magnitude. The marrow after 1 week of injections did not show a generalized myeloid hyperplasia, but did show an increase in eosinophils and a decrease in lymphocytes. Granulocyte- macrophage colony-stimulating factor plus granulocyte colony- stimulating factor (G-CSF) have been reported to synergize in vitro in both mouse and human bone marrow colony assays. However GM-CSF plus G- CSF in vivo, administered as either a single injection or as daily injections for 1 week, were found in the present study to induce, at most, an additive effect on circulating numbers of neutrophils. It is concluded that murine GM-CSF will be useful in the rat model to study the in vivo hematoreconstitutive effects of GM-CSF alone and in combination with other hematologic growth factors. The relatively rapid kinetics and lesser magnitude of GM-CSF-induced neutrophilia and monocytosis, as compared to G-CSF and M-CSF, respectively, and the lesser myeloproliferative effect of GM-CSF in bone marrow smears, as compared to G-CSF, might be taken to suggest that GM-CSF's natural activity is predominantly as an inflammatory rather than a myeloproliferative factor.

This article has been cited by other articles:

				G. Molineux, C. Hartley, P. McElroy, C. McCrea, P. Kerzic, and I. McNiece An Analysis of the Effects of Combined Treatment with rmGM-CSF and PEG-rHuMGDF in Murine Bone Marrow Transplant Recipients Stem Cells, January 1, 1997; 15(1): 43 - 49. [Abstract] [Full Text]