The effect of bone marrow depletion on prostaglandin E-producing suppressor macrophages in mouse spleen.
The i.p. injection of Corynebacterium parvum (CP) into CBA/J mice effected increases in macrophage colony-forming cells (M-CFC) when spleen cells were cultured with L cell culture filtrate as a source of colony-stimulating factor. Significant increases in phagocytic macrophages (M phi) with Fc receptors for IgG2a and IgG2b immune complexes were additionally noted among the spleen cells in these mice. These M phi effectively inhibited Con A-induced lymphocyte proliferation, probably reflecting a 10-fold increase above normal controls in prostaglandin E to 47 ng/3 X 10(6) spleen cells/ml. To determine whether the suppressor M phi are immediate derivatives of splenic M-CFC, we tried to induce suppressor M phi by the injection of CP into mice depleted of bone marrow M-CFC by the earlier administration of the bone-seeking isotope, 89Sr. This procedure reduced M-CFC in the bone marrow to less than 1% of normal for more than 30 days. Monocytes in the blood fell to 5% of normal by day 10 and were 30% on day 30. Levels of resident peritoneal M phi showed relatively little change in this period. By contrast, splenic M-CFC increased to 20-fold higher than the "cold" 88Sr controls. CP-induced suppressor M phi activity, however, was sharply reduced in 89Sr marrow-depleted mice on day 10, despite the striking increase in M-CFC. There was a threefold increase in the number of phagocytic M phi binding IgG2a immune complexes, with no significant increase in IgG2b binding M phi. The kinetics of recovery of suppressor M phi activity showed that on days 20, 30, and 50 after 89Sr injection the activities reached 20%, 30%, and 70% of the "cold" control, respectively, and correlated with the recovery of significant levels of M-CFC in the bone marrow. Taken together, these observations suggest that splenic M-CFC are not an immediate source of PGE-suppressor M phi in vivo. It appears more likely that the CP-inducible suppressor M phi, in particular, originate from radiosensitive bone marrow cells or require for differentiation a microenvironment provided by bone marrow cells. The data also suggest that the expression of the Fc gamma 2b receptor and of suppressor activity by CP-induced splenic M phi are related phenomena.
Shibata
Y
Y
Volkman
A
A
D000818:Animals; D001853:Bone Marrow / Q000473:pathology* / Q000528:radiation effects; D003114:Colony-Forming Units Assay; D005260:Female; D007165:Immunosuppression Therapy / Q000379:methods; D007970:Leukopenia / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D008262:Macrophage Activation / Q000528:radiation effects; D008264:Macrophages / Q000145:classification / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA; D011425:Propionibacterium acnes / Q000276:immunology; D011458:Prostaglandins E / Q000096:biosynthesis*; D011961:Receptors, Fc / Q000096:biosynthesis; D017452:Receptors, IgG; D013154:Spleen / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013326:Strontium Radioisotopes / Q000008:administration & dosage
D011458:Prostaglandins E; D011961:Receptors, Fc; D017452:Receptors, IgG; D013326:Strontium Radioisotopes