Stimulation of fibroblast chemotaxis by human recombinant tumor necrosis factor α (tnf-α) and a synthetic tnf-α 31-68 peptide

Arnold Postlethwaite, Jerome M. Seyer

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Macrophages are a major source of fibrogenic factors that promote healing of injured tissue. The recruitment of fibroblasts to sites of tissue injury is a prerequisite for optimal repair of tissue damage. In the present study, human recombinant tumor necrosis factor α (hrTNF-α), a major macrophage-derived cytokine, was demonstrated to be a potent fibroblast chemoattractant, inducing migration at picomolar concentrations. Anti-hrTNF-α monoclonal antibody neutralized most of the fibroblast chemotactic activity generated during short-term culture of human peripheral blood monocytes stimulated with bacterial lipopolysaccharide, suggesting that TNF-α is a major monocyte-derived fibroblast chemoattractant. The portion of the human TNF-α molecule responsible for its chemotactic stimulation of fibroblasts appears to reside in residues 31-68. This region is highly conserved between TNF-α and lymphotoxin. This peptide is not only itself chemotactic but is also able to block the chemotactic response of fibroblasts to hrTNF-α and vice versa, suggesting that they each mediate fibroblast migration through similar mechanisms. These data further underscore the potential importance of TNF-α in modulating a variety of fibroblast functions, including chemoacxis and synthesis ofcollagen, glycosaminoglycans, interleukin 1a (IL-1α) and -β, human histocompatibility leukocyte antigen A and B antigens, collagenase, prostaglandin E2, and ID6.

Original languageEnglish (US)
Pages (from-to)1749-1756
Number of pages8
JournalJournal of Experimental Medicine
Volume172
Issue number6
DOIs
StatePublished - Dec 1 1990

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Chemotaxis
Tumor Necrosis Factor-alpha
Fibroblasts
Peptides
Chemotactic Factors
Monocytes
Macrophages
Lymphotoxin-alpha
Histocompatibility Antigens
human TNF protein
Interleukins
Collagenases
HLA Antigens
Glycosaminoglycans
Dinoprostone
Lipopolysaccharides
Monoclonal Antibodies
Cytokines
Antigens
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Stimulation of fibroblast chemotaxis by human recombinant tumor necrosis factor α (tnf-α) and a synthetic tnf-α 31-68 peptide. / Postlethwaite, Arnold; Seyer, Jerome M.

In: Journal of Experimental Medicine, Vol. 172, No. 6, 01.12.1990, p. 1749-1756.

Research output: Contribution to journalArticle

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