Lymphotoxin lacks effects on 75-kDa receptors in cytotoxicity on U-937 cells

We examined differences in cytotoxic activity between human lymphotoxin (LT) and tumor necrosis factor (TNF) as functions of their interaction with two types of TNF receptors, 55-kDa (p55R) and 75-kDa (p75R). Cytotoxic activity of LT was much lower than that of TNF on a human monocytic cell line, U-937, on which p75R was predominant. Monoclonal antibodies specific for p55R (htr-5 and htr-9) and p75R (utr-1) significantly diminished TNF cytotoxicity, whereas, utr-1 was only slightly inhibitory to LT cytotoxicity, and htr-5 reduced it significantly. TNF individual binding to p75R increased cytotoxic activity when p55R was occupied by htr-9 and a mutein of TNF which significantly lost affinity to p75R. However, LT binding to p75R did not increase. Scatchard analysis with [125I]LT and [125I]TNF showed that LT still had approximately half of the affinity to p75R and slightly less affinity to p55R than TNF. These results indicate slight cytotoxicity of LT compared to TNF, due to inability of LT to signal through p75R on U-937 cells without significant loss of affinity to p75R.