Inducible macrophage cytotoxins. II. Tumor lysis mechanism involving target cell-binding proteases.

Abstract

Thioglycollate-elicited C57BL/6 peritoneal exudate macrophage monolayers (PEMM) stimulated with poly I . poly C or LPS released a macrophage cytotoxin (MCT) that rapidly bound to syngeneic (EL 4) or allogeneic (NS-1, YAC-1) tumor cells but did not bind to normal splenocytes. No binding to human (K562) tumor cells was observed. PEMM stimulated with poly I . poly C destroyed allogeneic tumor cells (NS-1) when separated by cell-impermeable Millipore filters in vitro; in contrast, PEMM not stimulated with poly I . poly C were incapable of lysing targets when separated by membranes. The reversible inhibitors N alpha-p-tosyl-L-arginine methyl ester and soybean trypsin inhibitor and the irreversible inhibitors N alpha-p-tosyl-L-lysine chloromethyl ketone and phenylmethylsulfonyl fluoride, of trypsin-like proteases, significantly or totally inhibited MCT cell-lytic activity for L-929 cells in vitro. Furthermore, modification of MCT-associated arginine residues by 1,2-cyclohexanedione completely blocked lytic activity. MCT was concluded to be an inducible nonspecific cell-lytic effector molecule elaborated by activated macrophages, which could bind to potential target cells, and was itself or was associated with a protease.

• Authors: T H Reidarson, G A Granger, J Klostergaard
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 69 Issue 4 Pg. 889-94 (Oct 1982) ISSN: 0027-8874 [Print] United States
• PMID: 6750198 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytotoxins
• Lipopolysaccharides
• Protease Inhibitors
• Peptide Hydrolases
• Poly I-C

Topics

• Animals
• Cell Line
• Cytotoxins (biosynthesis, isolation & purification)
• Lipopolysaccharides (pharmacology)
• Macrophage Activation (drug effects)
• Macrophages (drug effects, immunology)
• Mice
• Mice, Inbred Strains
• Neoplasms, Experimental (enzymology, immunology)
• Peptide Hydrolases (immunology, metabolism)
• Poly I-C (pharmacology)
• Protease Inhibitors
• Protein Binding
• Spleen (immunology)