SPLENIC MACROPHAGE ACTIVATION AND FUNCTIONS IN AMYLOID ENHANCING FACTOR-INDUCED SECONDARY AMYLOIDOSIS - STUDY OF PHAGOCYTOSIS, KILLING, RESPIRATORY BURST, AND MHC CLASS-II SURFACE EXPRESSION

Secondary amyloidosis is a systemic disease characterized by the extra cellular tissue deposition of insoluble fibrillar amyloid A protein. A berrant metabolism of serum amyloid A protein by reticuloendothelial c ells is thought to result in the accumulation of fibrils within the ti ssue. Treatment of mice with amyloid-enhancing factor (AEF) in conjunc tion with an inflammatory stimulus (i.e., AgNO3) induced amyloid depos ition within 48-72 h. The activation state of a macrophage largely def ines its enzymatic capabilities. In the studies reported here, we exam ined the effect of AEF on spleen macrophage activation using both func tional and phenotypic assays. We found that while AEF in the presence or absence of AgNO3 has no apparent effect on the ability of spleen an d liver macrophages to phagocytose or kill Listeria monocytogenes, it appears to block enhanced respiratory burst function (as measured by O 2- production) observed with AgNO3 alone. AEF therefore seems capable of inhibiting certain macrophage activation-associated functions while not affecting others. Our activation phenotype studies, using surface Ia expression, reveal that AEF blocks the increase in number of splen ic macrophages expressing la seen with AgNO3 alone. Treatment with int erferon-gamma was found to restore decreased Ia expression in animals given AEF + AgNO3 but did not prevent amyloid A fibril deposition.