Amphotericin B selectively stimulates macrophages from high responder mouse strains

Lymphoid cells from most inbred mouse strains respond to amphotericin B (AmB)-induced immunostimulation. However, C57BL/6 mice and related strains display low or absent lymphoid cell stimulation by AmB and enhanced susceptibility to AmB toxicity. Experiments reported here show that in vitro incubation with AmB can stimulate AKR (AmB-high responder strain) macrophage proliferation. Intraperitoneal injection of AKR mice with AmB also elicits a population of macrophages primed for enhanced oxidative burst activity after triggering by zymosan particles. Under the same experimental conditions, AmB elicits a population of very weakly responsive macrophages from C57BL/6 mice. The low responsiveness of C57BL/6 macrophages correlates with previous observations that AmB is a potent immunoadjuvant and B cell mitogen in most inbred strains, but it selectively lacks immunoadjuvant effects in C57BL/6 mice and it also fails to induce polyclonal B cell stimulation in their spleen cell suspensions. Similarly, in measurements of protein synthesis in vitro, high concentrations of AmB produce a greater inhibition of protein synthesis in C57BL/6 peritoneal macrophages than in parallel cultures of AKR macrophages. These findings support the hypothesis that the macrophage is an important target cell in the mediation of AmB-induced immunomodulation.