Effects of nicotine on the fine structure of cultivated mouse peritoneal macrophages.

Abstract

The effects of nicotine on the fine structure of thioglycollate-elicited mouse peritoneal macrophages cultivated in vitro was studied in order to elucidate further the mechanism behind its inhibitory effect on endocytosis and intracellular degradation of exogenous protein. In the concentrations (1.0-1,000 nM) and times (2-48 h) used here, nicotine lacked cytotoxic effect and did not appreciably affect the occurrence and distribution of different organelles. The most prominent change caused by the drug was the formation of large vacuoles believed to represent swollen lysosomes. This finding supports the idea that nicotine, like several other amines and weak bases, accumulates in the lysosomes by proton trapping. This could in turn impair the digestive capacity of the lysosomes by raising pH above the optimum of the acid hydrolases. It could also affect endocytosis and recycling of plasma membrane components. Additionally, the nicotine treatment led to an increased number of autophagic vacuoles consisting of lysosomes enclosing other lysosomes. A 'lysosomophagic' process of this type has previously been observed in other situations with decreased endocytosis. It is suggested to be a subtype of autophagy that serves the purpose of regulating the amount of lysosomes in connection with changes in the functional activity of this organelle.