A mechanism for the initiation of selective acid hydrolase secretion with macrophages by weak bases that is functionally independent of complement activation is proposed on the basis of the following findings. (1) The release of beta-galactosidase from macrophages exposed to methylamine and chloroquine was found to be highly dependent on the pH of the incubation medium; the degree of lysosomal secretion correlated closely with the amount of free base in solution at each pH investigated. (2) The secretion of beta-galactosidase induced by methylamine was additively enhanced by a fixed dose of zymosan; likewise, chloroquine additively enhanced the secretion of beta-galactosidase during exposure to zymosan. By contrast, chloroquine did not additively enhance the release of lysosomal enzyme affected by exposure to methylamine. (3) Two new secretagogues, imidazole and benzamidine, like chloroquine, failed to initiate any activation of the alternative complement pathway. The possible relationship between secretagogue induced vacuolization and lysosomal secretion is discussed.
