INHIBITION OF DAY-12 SPLEEN COLONY-FORMING-UNITS BY A MONOCLONAL-ANTIBODY TO THE MURINE MACROPHAGE MONOCYTE COLONY-STIMULATING FACTOR-RECEPTOR/

Primitive hematopoietic stem cells differentiate into committed progen itors that are thought to selectively express hematopoietic growth fac tor receptor(s), thereby acquiring hematopoietic growth factor respons iveness. To assess whether hematopoietic stem cells express hematopoie tic growth factor receptors, the progenitor activity of bone marrow (B M) fractions, isolated by expression of receptors for macrophage/monoc yte colony-stimulating factor (M-CSF), were examined. Recovery of day- 12 spleen colony-forming units (CFU-S) is diminished in both M-CSF rec eptor-positive (M-CSFR(+)) and M-CSFR(-) fractions, indicating antibod y inhibition of day-12 CFU-S. Incubation of BM cells with antibody wit hout fractionation inhibits 50% to 60% of day-12 CFU-S. This inhibitio n is specific (control antibodies have no effect) and reversible by re moval of bound antibody at low pH. Incubating BM cells with control or antireceptor antibody does not affect day-8 CFU-S, which are predomin antly erythroid. Treating sublethally irradiated mice with antibody in hibits endogenous day-12 CFU-S. These results indicate that some early progenitors express M-CSFRs, and blocking M-CSFRs inhibits the abilit y of these progenitors to form colonies, possibly because of inactivat ion caused by prolonged receptor blockade. (C) 1995 by The American So ciety of Hematology.