Absence of CSF-1 in macrophage-deficient op/op mice has differential effects on macrophage colony stimulating activity (M-CSA) released by various organs and cells.
The absence of detectable levels of CSF-1 in op/op mice results in a marked deficiency of macrophage colony-stimulating activity (M-CSA) in both the unstimulated and postendotoxin sera of these animals. These deficiences are not secondary to the presence of an inhibitor of macrophage formation. In contrast, various organs, particularly the organs of endotoxin-treated op/op mice, released amounts of M-CSA comparable to those of normal mice. Similarly, mitogen-stimulated lymphoid cells from op/op mice released either similar or increased amounts of M-CSA compared to mitogen stimulated +/+ lymphoid cells. On the other hand, conditioned media from cultures of fibroblastoid cells obtained from primary and secondary cultures of op/op organs were nearly totally devoid of M-CSA. However, incubation of these op/op fibroblasts with endotoxin in vitro induced the easily and readily detectable levels of M-CSA. These data suggest that CSF-1 is most likely a major source of M-CSA in serum and postendotoxin serum, while its contribution to soluble M-CSA in other organs may be only partial. In addition, in specific circumstances, the induced release of other macrophage growth factors may partially compensate for CSF-1 deficiency. Furthermore, it appears that the generalized macrophage deficiency in op/op mice cannot be fully explained by the deficiency of soluble M-CSA (soluble CSF-1) and argues for an in vivo role of membrane-bound CSF-1. These data may be interpreted as supporting a model in which the regulation of CSF-1-dependent and CSF-1-independent macrophage production is carried out by partly unrelated mechanisms.
Wiktor-Jedrzejczak
W
W
Department of Immunology, Military School of Medicine, Warsaw, Poland.
Sell
K W
KW
Szwech
P
P
Ahmed-Ansari
A
A
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D017077:Culture Media, Conditioned; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency*; D008264:Macrophages / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000378:metabolism; D009924:Organ Culture Techniques; D012867:Skin / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism
D017077:Culture Media, Conditioned; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor