COMPARISON OF METABOLISM OF ALVEOLAR MACROPHAGES FROM HUMANS, RATS, AND RABBITS - RESPONSE TO HEAT-KILLED BACTERIA OR PHORBOL MYRISTATE ACETATE

Abstract

Metabolic activities of unstimulated or stimulated AM [alveolar macrophage] from humans, rats and rabbits were examined and compared in vitro. Rates of O2 consumption, chemiluminescence and glucose (1- or 6-14C) oxidation by unstimulated AM from these 3 species increased following stimulation of the AM by bacteria or PMA [phorbol myristate acetate]. Although the absolute metabolic responses of AM from humans, rats or wild rabbits were different, the metabolic activities from each species were nearly identical when compared on the basis of protein content of the cells. In contrast to the enhanced biochemical responses of AM from humans, rats or wild rabbits, stimulated AM from certain commercially supplied rabbits failed to increase their metabolism. The failure of AM from these rabbits to respond metabolically was probably due to an acquired abnormality resulting from their care and storage at the supplier. The defect was associated with the presence of large numbers of Bordetella bronchiseptica organisms in the lavage effluents from these commercially supplied rabbits. This abnormality in metabolism of AM was reversed following prolonged residence of the rabbits in the laboratory, and the correction of the defect was accompanied by a disappearance of B. bronchiseptica from the lavage fluid. The results comprehensively compare and contrast the metabolism of AM from humans and animals and emphasize the need to document the appropriateness of animal models before using them to predict biologic reactions of humans.