THE TNF RECEPTORS P55 AND P75 MEDIATE CHEMOTAXIS OF PMN INDUCED BY TNF-ALPHA AND A TNF-ALPHA-36-62 PEPTIDE

THE present study was performed to examine whether residues 36-62 of T NF alpha contain the chemotactic domain of TNF alpha, and whether the p55 and p75 TNF receptors are involed in TNE alpha induced chemotaxis. The chemotactic effect of TNF alpha On PMN was inhibited by the mAbs Hrt-7b and Utr-1, against the p55 and p75 TNF receptors, respectively. Both receptors may therefore be required for mediating the chemotacti c effect of TNF alpha. The synthetic TNF alpha 36-62, similar to TNF a lpha, had chemotactic effects on both PMN and monocytes. The chemotact ic activity of the TNF alpha 36-62 peptide on PMN, was inhibited by Ht r-7b, Utr-1 and soluble p55 receptor, which shows that the peptide pos sessed the ability to induce chemotaxis through the TNF receptors. In contrast to TNF alpha, the peptide did not show a cytotoxic activity a gainst WEHI 164 fibrosarcoma cells. It is suggested that different dom ains of the TNF alpha molecule induce distinct biological effects.