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-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.
Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
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Morzycki
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Issekutz
D015815:Cell Adhesion Molecules / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000096:biosynthesis; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects*; D014176:Protein Biosynthesis; D013268:Stimulation, Chemical; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D002630:Chemotactic Factors; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha