Inhibition of Phagocytosis and Glucose Metabolism of Alveolar Macrophages during Pulmonary Tumour Growth

Abstract

Alveolar macrophage (AM) phagocytic activity and glucose metabolism were evaluated during lung tumour growth in adult rats challenged i.v. with 10⁵ viable Walker 256 tumour cells. Phagocytosis was estimated by the in vitro uptake of ¹⁴C-labelled Pseudomonas aeruginosa and glucose oxidation was evaluated by ¹⁴CO₂ production from 1-¹⁴C-glucose. AM were harvested by lung lavage from rats prior to and at 7 and 21 days following i.v. tumour-cell challenge. Macroscopic lung tumour nodules were not observed by 7 days after tumour challenge. However, 3 weeks after tumour challenge, tumour nodules were clearly identifiable on the surfaces of the lungs. One week after the i.v. tumour challenge a marked increase in the number of AM was evident. The in vitro phagocytosis of ¹⁴C-labelled Pseudomonas aeruginosa was unaltered at that time, but became progressively depressed thereafter. Three weeks after tumour challenge, this decrease in phagocytic activity was evident when cells were incubated in normal serum, and was furtheri ntensified by serum obtained from tumour-bearing animals. Glucose oxidation by AM in either the resting condition or during bacterial phagocytosis was clearly decreased at both 1 and 3 weeks following i.v. tumour challenge. These findings indicate that the growth of pulmonary metastases is associated with a depression of alveolar macrophage bacterial phagocytic capacity, perturbations in serum opsonic activity and distinct alterations in macrophage energy metabolism. The metabolic dysfunction may impair pulmonary macrophage host defences against lung tumour growth.