INVITRO INDUCTION OF TUMOR NECROSIS FACTOR-ALPHA, TUMOR CYTOLYSIS, AND BLAST-TRANSFORMATION BY SPIROPLASMA MEMBRANES

Membranes of Spiroplasma sp. strain MQ-1 (hereafter referred to as MQ-1) were potent inducers of tumor necrosis factor α (TNFα) secretion and of blast transformation. Specific anti-recombi-nant murine TNFα antibodies markedly inhibited macrophage-mediated tumor cytolysis of A9 fibrosarcoma target cells following activation by MQ-1 membranes. Thus, TNFα plays a major role in mediation of tumor cytolysis induced by MQ-1 membranes, which is similar to its role in lipopolysaccharide (LPS)-induced tumor cytolysis. Two findings, however, suggested that the mechanism of macrophage activation by MQ-1 membranes differs from that by LPS: (a) macrophages, taken from C3H/HeJ mice showing a low responsiveness to LPS, were activated by MQ-1 membranes to enhanced TNFα secretion, resulting in a high-level tumor cytolysis compared with the negligible tumor cytolysis induced by LPS; and (b) MQ-1 membranes and LPS synergjzed to highly augment TNFα secretion by macrophages of C57BL/6 mice. MQ-1 membranes were capable of inducing blast transformation of murine lymphocytes as well. In addition, they activated human monocytes to secrete high levels of TNFα. Further studies need to be carried out using in vivo models to evaluate the therapeutic potential of MQ-1 membranes in the treatment of malignant diseases. © 1990 Oxford University Press.