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Tumoricidal Effector Mechanisms of Murine BCG‐Activated Macrophages: Role of TNF in Conjugation‐Dependent and Conjugation‐Independent Pathways
Author(s) -
Klostergaard Jim,
Stoltje Paul A.,
Kull Frederick C.
Publication year - 1990
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.48.3.220
Subject(s) - cytolysis , tumor necrosis factor alpha , effector , biology , macrophage , secretion , lipopolysaccharide , macrophage activating factor , antiserum , microbiology and biotechnology , lysis , receptor , immunology , in vitro , cytotoxicity , antibody , biochemistry
The roles of secreted and membrane‐associated TNFs were investigated in activated macrophage cytolysis of L929, EMT‐6, and P815 targets. While all three targets were susceptible to cytolysis in coculture, an anti‐TNF antiserum blocked lysis of L929 and EMT‐6 but not of the P815 targets. Of the three targets, recombinant human or mouse TNF could only lyse the L929 target; despite the fact that a role for TNF was invoked in lysis of EMT‐6 targets in coculture, the latter was strongly resistant to soluble rTNF, even at concentrations 30–40‐fold higher than the K a for Its TNF‐receptor. Cytolysis of the L929 target occurred when it was cocultured with BCG‐activated macrophages even when these effector cells did not secrete TNF, either due to prior chemical crosslinking or to lack of exposure to a triggering level of lipopolysaccharide. Furthermore, by introduction of the anti‐TNF antiserum over a dose‐range, it was shown that macrophage cytolysis both of L929 and EMT‐6 targets occurred in the absence of bioavailable, fluid‐phase TNF. Thus, even for targets susceptible to fluid‐phase TNF, TNF‐dependent, direct macrophage‐mediated cytolysis appears to be a function independent of secreted TNF and one that utilizes effector‐target contact to express the action of a membrane form of the molecule.