Histamine synthesis by non-mast cells through mitogen-dependent induction of histidine decarboxylase

Culture of spleen cells of C57BL/6 mice led to a spontaneous increase in activity of histidine decarboxylase (HDC) in the cell and the medium. Concomitantly histamine increased in the cells and, especially, in the medium. Addition of concanavalin A (Con A) or lipopolysaccharide (LPS) to the culture enhanced these processes. There was also a significant Con A-dependent increase in HDC activity and histamine biosynthesis in the culture of spleen cells of genetically mast-cell deficient W/Wv mice. Peritoneal macrophages of C57BL/6J mice had constitutively 11-19-fold as much HDC as T and B lymphocytes when compared on the basis of same number of cells. Con A had no effect on HDC activity when the macrophages were cultured alone. However, co-culture with T lymphocytes, separated from macrophages by a millipore filter membrane (pore size, 0.45 micron), rendered the macrophages responsive to Con A, leading to a notable increase in HDC activity in the cell. Addition of LPS caused a small but significant increase in HDC activity in macrophages, even when the cells were cultured alone. Co-culture with T or B cells enhanced the LPS-dependent increase in HDC activity in macrophages. In contrast, the HDC activity in T and B lymphocytes did not change essentially in the presence of any of these mitogens, even when they were co-cultured with macrophages. These results suggest that histamine is synthesized by non-mast cells through HDC.