Tumour necrosis factor-alpha but not interleukin-1 induces polymorphonuclear leucocyte migration through fibroblast layers by a fibroblast-dependent mechanism

Interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-α) both induce polymorphonuclear leucocyte (PMNL) infiltration into tissues and they have a synergistic action in this respect. We and others have observed that IL-1α and TNF-α 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-α, but not IL-1α, 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-α 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-α 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 suggest a distinct activation by TNF-α of fibroblasts to facilitate PMNL migration through fibroblast barriers. These findings may in part account for the synergistic action of IL-1 and TNF-α in inducing extravascular accumulation of PMNL during inflammation.