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Lymphokine-independent, Leukemia Cell-mediated Induction of Tumor Necrosis Factor in Human Monocytes¹

Department of Microbiology, Ehime University School of Medicine, Shigenobu, Ehime 791-02, Japan

Unactivated human blood monocytes and monocytic THP-1 cells were found to respond to some leukemia cells by tumor necrosis factor (TNF) production. The TNF production by THP-1 cells in response to K562 cells was preceded by a rapid rise in [Ca²⁺]_i, initiated within 1 h and terminated within 4 h as a refractory state took over. Neither the amount nor the duration of TNF production was enhanced by -interferon. The P32/ISH cells did not induce a significant [Ca²⁺]_i change of TNF production, while MOLT-4 cells failed to induce TNF despite their capacity to mobilize Ca²⁺ in THP-1 cells. The failure of P32/ISH or MOLT-4 to induce TNF was attributed primarily to a lack of stimulatory membrane molecules rather than to suppression by an inhibitory component, since liposomes carrying membrane components of K562 and MOLT-4 or P32/ISH in varying proportions elicited TNF production that precisely reflected the K562 proportion. The ability of K562 to induce TNF was selectively impaired by trypsin, whereas the ability to mobilize [Ca²⁺]_i was more sensitive to glutaraldehyde, although once the latter activity was extinguished, the K562 cell could no longer induce TNF. These results suggest that some leukemia cells are equipped with two or more signaling membrane moieties which together stimulate monocytes for transient tumoricidal expression in the preimmune stage.

¹ This study was in part supported by grants from the Ministry of Education, Science and Culture, Japan, and the Ehime Health Foundation.

² Present address: Department of Clinical Pathology, Ehime College of Health Science, Tobe, Ehime 791-11, Japan.

³ To whom requests for reprints should be addressed.

Received 10/ 6/89. Revised 1/ 4/90.