Mast cells induce activation of human lung fibroblasts in vitro

Ekaterina Garbozenko, Ilaria Puxeddu, Francesca Levi-Schaffer*, Neville Berkman, Mordechai Kramer, Arnon Nagleir

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Mast cells are able to induce proliferation of skin fibroblasts; however, their effect on lungfibroblasts has not been clearly established. Using in vitro cocultures of rat or human mast cells with lung fibroblasts, the authors determined whether mast cells alter proliferation, collagen synthesis, and metalloproteinase production from lung fibroblasts. Mast cells enhanced the proliferation of human fibroblasts (mean ± SEM: 90% ± 4.7% increase, P < .001) while inhibiting fibroblast collagen synthesis (48.1% ± 4.2% decrease, P < .001). Histamine, but not tryptase, significantly enhanced fibroblast proliferation: 92% ± 5.8% (P < .001) and 39.2% ± 4.3% (P > 0.05), respectively. Rat mast cell sonicate added to lung fibroblasts induced the activation of metalloproteinase-9 while inhibiting that of metaloproteinase-2. The addition of lipopolysaccharide (LPS)-stimulated lung macrophage supernatant further enhanced the proliferative effect of mast cells on fibroblasts (by 60% ± 7.8%, P < .001) and induced synthesis of collagen from these cells (190% ± 28% increase versus control, P < .05). This study demonstrates that mast cells influence several aspects of lung fibroblast function in vitro.

Original languageEnglish
Pages (from-to)705-721
Number of pages17
JournalExperimental Lung Research
Volume30
Issue number8
DOIs
StatePublished - Dec 2004
Externally publishedYes

Keywords

  • Fibroblast
  • Fibrosis
  • Lung
  • Macrophage
  • Mast cell

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