REGULATION OF NEUTROPHIL MIGRATION AND SUPEROXIDE PRODUCTION BY RECOMBINANT TUMOR NECROSIS FACTORS-ALPHA AND FACTOR-BETA - COMPARISON TO RECOMBINANT INTERFERON-GAMMA AND INTERLEUKIN-1-ALPHA

  • 1 October 1987
    • journal article
    • research article
    • Vol. 70  (4) , 979-984
Abstract
We compared the ability of recombinant human tumor necrosis factor-.alpha. (rHuTNF-.alpha.) and tumor necrosis factor-.beta. (rHuTNF-.beta.) to stimulate polymorphonuclear neutrophil (PMN) migration and superoxide production. Significant PMN migration occurred across polycarbonste filters after stimulation with rHuTNF-.alpha. at concentrations ranging from 10-7 to 10-10 mol/L for rHuTNF-.beta. and N-formylmethionyl-leucyl phenylalanine (FMLP), whereas recombinant human interferon-.gamma. was only minimally active at 10-7 mol/L and recombinant human interleukin-1.alpha. was inactive at the doses tested. In addition, antibodies to rHuTNF-.alpha. completely inhibited rHuTNF-.alpha. but not rHuTNF-.beta. or FMLP-induced PMN migration. Combinations of rHuTNF-.alpha. and rHuTNF-.beta. (at similar molar concentrations) stimulated PMN migration levels comparable to that obtained with rHuTNF-.alpha. alone. Checkerboard analyses performed by placing different concentrations of rHuTNF-.alpha. and rHuTNF-.beta. above and below polycarbonate filters of microchemotaxis chambers demonstrated that rHuTNF-.alpha. and rHuTNF-.beta. stimulated both chemotactic and chemokinetic responses by PMN. Additional studies demonstrated that 1 .times. 108 mol/L rHuTNF-.alpha. and 3 .times. 10-9 mol/L rHuTNF-.beta. (which respresents 104 U/mL of each cytokine) were similar in their ability to induce superoxide production by PMNs; however, at ten- to 100-fold lower molar concentration (103 and 102 units), rHuTNF-.alpha. was significantly more active than rHuTNF-.beta.. At the doses tested, both cytokines were less active than phorbol myristate acetate at stimulating O2- release. The results demonstrate that rHuTNF-.alpha. and rHuTNF-.beta. differ quantitatively but not qualitatively in their effects of PMN functions in vitro and suggest that rHuTNF-.beta. may be less toxic than rHuTNF-.alpha. in vivo.

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