The effects of eosinophil-granule major basic protein on lung-macrophage superoxide anion generation.

The effects of major basic protein (MBP) on superoxide anion release in vitro from normal guinea pig (GP) alveolar macrophages (AM) was determined. Native MBP at 55 micrograms/ml had an immediate effect (reduction) on phorbol myristate acetate (PMA)-induced (p less than 0.01) and spontaneous (p = 0.055) superoxide (O2-) release by GP AMs. A similar effect was not observed from AMs incubated for 24 hours with MBP before assessment of O2- release. However, after AMs were incubated with MBP for 48 hours, again there was a significant reduction observed in both PMA-induced (p = 0.01) and spontaneous (p = 0.002) O2- release compared to that of control cultures. The immediate effect of MBP on AM O2- release was not due to cytotoxicity of MBP for AM. In contrast, the effect observed after 48 hours of culture was due, in part, to a direct toxic effect of the MBP on the AM because the viability of AM cultured for 48 hours with MBP (55 micrograms/ml) was 63.6% +/- 13% compared to the viability of control cultures of AM that was 83.9% +/- 7%; p = 0.03. The effect of MBP on AM O2- release at 48 hours was progressive over concentrations ranging from 2 to 55 micrograms/ml. These data suggest that native MBP can affect adversely PMA-induced and spontaneous release of O2- by GP AMs and that this effect depends only in part on the cytotoxic properties of MBP.