TY - JOUR
T1 - Modification of macrophage differentiation
T2 - Dimethylnitrosamine induced alteration in the responses towards the regulatory signals controlling myelopoiesis
AU - Myers, Michael J.
AU - Schook, Lawrence B.
N1 - Funding Information:
Acknowledgements -- The authors would like to acknowledge the excellent technical assistance of Cathy S. Dickens. We wish to thank Patty Lee and Maria Sweetser for their patience and efforts in preparing this manuscript. The authors would also like to thank Dr E. Richard Stanley (Department of Microbiology and Immunology, Albert Einstein College of Medicine) for his generous gift of the goat anti-L929 CSF-I. This work was supported by a grant from NIH (ES-03468).
PY - 1987
Y1 - 1987
N2 - Results from our laboratory have demonstrated that the alteration in cellular immunity (CMI) resulting from exposure to dimethylnitrosamine (DMN) in vivo is due to changes in myelopoiesis. Bone marrow stem cells showed no alterations in their capacity to generate CFU-S (pleuripotent stem cells) nor were there any changes in the number of CFU-Mix colonies (IL-3 responsive stem cells) arising from the bone marrow of DMN exposed mice. However, the generation of G/M-CSF and CSF-1 responsive colonies (CFU-G/M and CFU-M) were altered, resulting in an increase in the number of colonies. G/M-CSF colonies generated from the bone marrow stem cells obtained from DMN exposed mice also had increased numbers of cells produced by each colony (total cells/CFU). Indirect immunofluorescence studies demonstrated no changes in the granulocyte/macrophage subsets following G/M-CSF stimulation of bone marrow stem cells obtained from DMN exposed mice. However, there was no change in the total number of cells generated by CSF-1 from the marrows of DMN exposed mice as compared to vehicle treated mice. Marrow cells from DMN exposed mice cultured in vitro with G/M-CSF showed both a shift in their peak proliferative response from 48-72 h to 30-60 h and an increased proliferative response. These same marrow cells showed no shift in their kinetics but a decrease in their proliferative response to CSF-1. Examination of the sera from DMN exposed mice for alterations in the regulatory factors controlling myelopoiesis demonstrated a net decrease of CSF-1 activity but no changes in the concentrations of two inhibitory factors, transferrin and lactoferrin. These results indicate DMN exposure is affecting macrophage myelopoiesis at the level of the G/M-CSF and CSF-1 responsive cells through: (1) alterations in the responsiveness of these cells to the growth factor(s) and (2) changes in serum borne regulatory factors controlling myelopoiesis.
AB - Results from our laboratory have demonstrated that the alteration in cellular immunity (CMI) resulting from exposure to dimethylnitrosamine (DMN) in vivo is due to changes in myelopoiesis. Bone marrow stem cells showed no alterations in their capacity to generate CFU-S (pleuripotent stem cells) nor were there any changes in the number of CFU-Mix colonies (IL-3 responsive stem cells) arising from the bone marrow of DMN exposed mice. However, the generation of G/M-CSF and CSF-1 responsive colonies (CFU-G/M and CFU-M) were altered, resulting in an increase in the number of colonies. G/M-CSF colonies generated from the bone marrow stem cells obtained from DMN exposed mice also had increased numbers of cells produced by each colony (total cells/CFU). Indirect immunofluorescence studies demonstrated no changes in the granulocyte/macrophage subsets following G/M-CSF stimulation of bone marrow stem cells obtained from DMN exposed mice. However, there was no change in the total number of cells generated by CSF-1 from the marrows of DMN exposed mice as compared to vehicle treated mice. Marrow cells from DMN exposed mice cultured in vitro with G/M-CSF showed both a shift in their peak proliferative response from 48-72 h to 30-60 h and an increased proliferative response. These same marrow cells showed no shift in their kinetics but a decrease in their proliferative response to CSF-1. Examination of the sera from DMN exposed mice for alterations in the regulatory factors controlling myelopoiesis demonstrated a net decrease of CSF-1 activity but no changes in the concentrations of two inhibitory factors, transferrin and lactoferrin. These results indicate DMN exposure is affecting macrophage myelopoiesis at the level of the G/M-CSF and CSF-1 responsive cells through: (1) alterations in the responsiveness of these cells to the growth factor(s) and (2) changes in serum borne regulatory factors controlling myelopoiesis.
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U2 - 10.1016/0192-0561(87)90078-6
DO - 10.1016/0192-0561(87)90078-6
M3 - Article
C2 - 3323077
AN - SCOPUS:0023502052
SN - 0192-0561
VL - 9
SP - 817
EP - 825
JO - International Journal of Immunopharmacology
JF - International Journal of Immunopharmacology
IS - 7
ER -