Inhibition of osteoclastic activity by anti-MIP-1α antibodies in myeloma-bearing mice. (A) Functional blockade of MIP-1α activity inhibited osteoclast formation and activity in tumor-bearing mice. Representative serial sections of tibiae of anti-MIP-1α antibody- and isotype IgG-treated mice stained with H&E (top row) or for TRAP activity (bottom row) were chosen to illustrate clear differences in osteoclast number and activity even when extent of tumor infiltration of marrow cavities was comparable. Note overall reduction in the number of osteoclasts and intensity of TRAP staining in the anti-MIP-1α section (right column), compared with the isotype IgG-treated section (left column). In the latter, osteoclasts are present not only on the primary spongiosum aspect of the growth plate (asterisks) but also along the endocortical surface (arrows). In contrast, in the anti-MIP-1α section, no osteoclasts are present on the endocortical surface and very few can be seen even where the tumor is apposed to the growth plate. Original magnification, × 10. T indicates tumor; m, marrow. (B) Histomorphometric analysis of osteoclast activity in bones of mice treated with anti-MIP antibodies or isotype-matched antibodies/PBS. Neutralization of MIP-1α bioactivity reduced osteoclast activity expressed either as total number of TRAP+ multinucleated osteoclasts aligned along the tumor-bone interface (left panel) or as number of osteoclasts per millimeter of tumor-bone interface (right panel).