Divergent effects of the major mast cell products histamine, tryptase and TNF-alpha on human fibroblast behaviour.
Fibroblast proliferation is a key process in tissue remodeling and mast cells (MCs) are thought to play a crucial role. Having established that the three major MC products, tryptase, histamine and TNF-alpha (TNF) are normally present in human skin MCs, which are in close proximity to dermal fibroblasts, we studied their individual effects on cell cycle-controlled human dermal fibroblasts (HFFF2). These cells express receptors (H1, PAR2, TNFR1/2) for the major MC mediators, but only tryptase or a PAR2 agonist peptide stimulated proliferation and gene expression. TNF was antimitotic, and histamine, while elevating intracellular Ca2+ levels at high concentrations, did not affect proliferation. We conclude that MC products but also composition and numbers of respective receptors on fibroblasts are crucially responsible for fibroproliferative events.
Albrecht
M
M
Institute of Anatomy, Ludwig-Maximilians-University, Biedersteiner Strasse 29, 80802, Munich, Germany.
Frungieri
M B
MB
Kunz
L
L
Rämsch
R
R
Meineke
V
V
Köhn
F M
FM
Mayerhofer
A
A
D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression; D006632:Histamine / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D044464:Receptor, PAR-2 / Q000819:agonists / Q000235:genetics; D012016:Reference Values; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D012867:Skin / Q000166:cytology; D013997:Time Factors; D053802:Tryptases; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*
D010455:Peptides; D044464:Receptor, PAR-2; D014409:Tumor Necrosis Factor-alpha; D006632:Histamine; D012697:Serine Endopeptidases; D053802:Tryptases