Proliferation of erythromycin-stimulated mouse peritoneal macrophages in the absence of exogenous growth factors.
Erythromycin (0.2-20 micrograms/ml) induced the proliferation of macrophages of mouse peritoneal exudate cells (PEC) in a liquid medium without exogenous growth factors. The proliferating macrophages formed giant colonies between days 22 and 26 of culture; these colonies continued to proliferate even after subculture. The erythromycin-induced cell proliferation was independent of fibroblasts, T cells, B cells, or endotoxins. This activity seemed to be specific to erythromycin since other antibiotics such as tetracycline, streptomycin, gentamicin, penicillin G, and josamycin did not induce the proliferation of macrophages. Any known cytokines, including IL-2, IL-3, IL-4, IL-6, and GM-CSF, were not detectable by ELISA tests in any of the culture supernatants sampled from day 7 through day 28. The culture supernatants, however, had the capability of inducing the growth of macrophages, only in the presence of bioactive erythromycin at concentrations higher than 1.6 micrograms/l. Moreover, the culture supernatants, sampled after giant colonies had been formed, were capable of inducing giant colonies in the culture of adherent PEC. Thus, the erythromycin-induced macrophage proliferation might be due to the direct effect of this antibiotic, whereas the formation of giant colonies might be due to the production of some unidentified soluble factor produced by the proliferating macrophages. These data indicate that mouse PEC contain a subset of peritoneal macrophages capable of responding to erythromycin by forming proliferating colonies without exogenous growth factors.