Deactivation of primed respiratory burst response of goldfish macrophages by leukocyte-derived macrophage activating factor(s).

Macrophage activation factors (MAF), induced maximal priming of the respiratory burst response in GMCL after 6 h of stimulus, but by 24 or 48 h no priming effect was observed. Bacterial lipopolysaccharide (LPS) also primed the respiratory burst of goldfish macrophages, but the kinetics of priming were different from that induced by MAF. LPS induced a gradual increase in priming potential over 48 h of cultivation. Co-stimulation of macrophages with MAF and LPS resulted in enhanced priming of respiratory burst activity compared to either factor alone; however, the kinetics of priming were similar to those induced by MAF only. The MAF antagonized the ability of LPS to prime the respiratory burst over extended cultivation. The priming kinetics of the respiratory burst induced by MAF and/or LPS were not unique to GMCL, but were also similar for primary cultures of IVDKM. Respiratory burst deactivated macrophages-mounted potent nitric oxide response, indicating that this deactivation event was selective for respiratory burst activity. Autocrine factors produced by MAF-activated macrophages augmented priming of the respiratory burst, suggesting that deactivation of primed respiratory burst responses was not due to cytokine mediators produced by activated macrophages, but was most likely an intracellular deactivation event. Furthermore, production of reactive intermediates by activated fish macrophages was biphasic; with maximal ROI production occurring 6 h after stimulus, and maximal RNI occurring 72 h after stimulus. Our results indicate that activated fish macrophages mount sequential antimicrobial responses that are selectively deprogrammed once maximal induction has occurred. The ability to selectively deactivate ROI production without affecting subsequent RNI production may play an important role in host defense: regulating the duration of ROI production, and thus minimizing host tissue damage in an otherwise futile attempt to eliminate ROI resistant pathogens.