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 re spiratory burst response in GMCL after 6 h of stimulus, but by 24 or 4 8 h no priming effect was observed. Bacterial lipopolysaccharide (LPS) also primed the respiratory burst of goldfish macrophages, but the ki netics of priming were different from that induced by MAE LPS induced a gradual increase in priming potential over 48 h of cultivation. Go-s timulation of macrophages with MAF and LPS resulted in enhanced primin g of respiratory burst activity compared to either factor alone; howev er, 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 bu rst induced by MAF and/or LPS were not unique to GMCL, but were also s imilar for primary cultures of IVDKM. Respiratory burst deactivated ma crophages-mounted potent nitric oxide response, indicating that this d eactivation event was selective for respiratory burst activity. Autocr ine factors produced by MAF-activated macrophages augmented priming of the respiratory burst, suggesting that deactivation of primed respira tory burst responses was not due to cytokine mediators produced by act ivated macrophages, but was most likely an intracellular deactivation event. Furthermore, production of reactive intermediates by activated fish macrophages was biphasic; with maximal ROI production occuring 6 h after stimulus, and maximal RNI occuring 72 h after stimulus. Our re sults indicate that activated fish macrophages mount sequential antimi crobial responses that are selectively deprogrammed once maximal induc tion has occured. The ability to selectively deactivate ROI production without affecting subsequent RNI production may play an important rol e in host defense: regulating the duration of ROI production, and thus minimizing host tissue damage in an otherwise futile attempt to elimi nate ROI resistant pathogens. Copyright (C) 1996 Elsevier Science Ltd.