Tumour Necrosis Factor-Alpha but Not interleukin-1 Induces Polymorphonuclear Leucocyte Migration Through Fibroblast Layers by a Fibroblast-Dependent Mechanism

Immunology. 1991 Sep;74(1):107-13.

Abstract

Interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha) both induce polymorphonuclear leucocyte (PMNL) infiltration into tissues and they have a synergistic action in this respect. We and others have observed that IL-1 alpha and TNF-alpha induce 51Cr-labelled PMNL migration across monolayers of umbilical vein endothelium via an endothelial cell-dependent mechanism. Here we investigated the interaction of PMNL with fibroblasts, since PMNL probably encounter such cells in many tissues once they traverse the vascular wall. TNF-alpha, but not IL-1 alpha, was found to activate fibroblast monolayers, grown on polycarbonate filters, to stimulate PMNL transfibroblast migration. This was a time- and fibroblast-dependent process which required fibroblast protein synthesis, as indicated by inhibition with cycloheximide. The effect of TNF-alpha was not related to fibroblast chemotactic factor production (primarily IL-8), or to ICAM-1 up-regulation, since IL-1 was as active as TNF-alpha in this respect, without activating fibroblasts to support PMNL transfibroblast migration. Antiserum to IL-8, present during the assay, did not inhibit PMNL migration across the monolayers. The PMNL migration was highly dependent on the function of both CD11a (LFA-1) and CD11b (MAC-1) PMNL adhesion molecules, since monoclonal antibodies to either inhibited migration by about 80%. The results suggest a distinct activation by TNF-alpha of fibroblasts to facilitate PMNL migration through fibroblast barriers. These findings may in part account for the synergistic action of IL-1 and TNF-alpha in inducing extravascular accumulation of PMNL during inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion Molecules / physiology
  • Cell Movement / drug effects
  • Cells, Cultured
  • Chemotactic Factors / biosynthesis
  • Fibroblasts / immunology*
  • Fibroblasts / metabolism
  • Humans
  • Interleukin-1 / pharmacology*
  • Neutrophils / drug effects*
  • Protein Biosynthesis
  • Stimulation, Chemical
  • Time Factors
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Cell Adhesion Molecules
  • Chemotactic Factors
  • Interleukin-1
  • Tumor Necrosis Factor-alpha