Mast cells induce activation of human lung fibroblasts in vitro.
Mast cells are able to induce proliferation of skin fibroblasts; however, their effect on lung fibroblasts 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 poliferative 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.
Garbuzenko
Ekaterina
E
Department of Pharmacology, Hadassah-Hebrew, University Medical Center, Jerusalem, Israel.
Berkman
Neville
N
Puxeddu
Ilaria
I
Kramer
Mordechai
M
Nagler
Arnon
A
Levi-Schaffer
Francesca
F
D002457:Cell Extracts / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D005355:Fibrosis / Q000503:physiopathology*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D012697:Serine Endopeptidases / Q000494:pharmacology; D013010:Sonication; D053802:Tryptases
D002457:Cell Extracts; D008070:Lipopolysaccharides; D061965:Matrix Metalloproteinase Inhibitors; D006632:Histamine; D003094:Collagen; D012697:Serine Endopeptidases; C509223:Tpsab1 protein, rat; C509221:Tpsb2 protein, rat; D053802:Tryptases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9