Normal mouse lung tissue produces a growth-inhibitory factor(s) preferential for mouse monocytic leukemia cells.

Abstract

A growth-inhibitory (GI) factor, that specifically inhibits the growth of mouse monocytic leukemia cells, was found in conditioned medium of mouse lung tissue, but not in that of mouse brain, heart, liver, or kidney tissue. Conditioned medium of spleen or bone marrow cells had low GI activity. Pulmonary macrophages were as active as peritoneal and bone-marrow-derived macrophages in production of the GI activity. The GI factor inhibited the growth of murine monocytic leukemia cell lines Mm-A and J774.1, but scarcely inhibited the growth of other mouse cell lines, such as a myeloblastic leukemia cell line (M1), a Friend erythroleukemia cell line (745A) and a mammary carcinoma cell line (FM3A). It had no significant effect on the growth of human monocytic leukemia cell lines U937 and THP-1 or on the HL-60 promyelocytic leukemia cell line. These results suggest that the GI factor produced by mouse lung tissue preferentially inhibits the growth of mouse monocytic cells. The GI factor was found to be a proteinaceous substance with a molecular mass of 25 kDa. On chromatofocusing, the GI activity was eluted with Polybuffer 96/acetic acid at pH 7.2-7.5. The GI activity was not significantly decreased by heat treatment at 56 degrees C for 30 min or acid treatment (0.01 M HCl, 14 h), but the GI activity in glycosidase-treated conditioned medium of lung tissue was lost on heat treatment. The GI activity could not be neutralized with anti-(interferon alpha + beta) antibody. The activity was produced constitutively by lung tissues and its production was not stimulated appreciably by lipopolysaccharide, lectin, or poly(I).poly(C). The GI factor appears to be a cytokine unrelated to known cytokines such as tumor necrosis factor, interleukin-1, transforming growth factor beta, and interferons. These results suggest that the GI factor may be involved in negative feedback regulation of macrophage production in steady-state conditions in the lungs.