Co-cultured human mast cells stimulate fibroblast-mediated contraction of collagen gels.
In the current study, we asked whether mast cells might modulate remodeling of extracellular matrix by affecting fibroblast-mediated contraction of three-dimensional collagen gels. Mast cells and human lung fibroblasts were co-cultured in floating type I collagen gels. The area of the gels was measured by an image analyzer. Mast cells in co-culture augmented fibroblast contractility (P < 0.001) in a time- and concentration dependent manner. The tryptase inhibitor bis(5-amidino-2-benzimidazo-lyl)methane (BABIM) were unable to block the augmented fibroblast contractility induced by co-cultured mast cells and tryptase added alone in the culture system had no effect on contractility, suggesting that other mediators besides tryptase might be involved. The amount of collagen in dissolved gels, measured as hydroxyproline, did not change after co-culture indicating that degradation of collagen may not be a major mechanism. Our findings support the hypothesis that the activity of mast cells may drive rearrangement of extracellular matrix and this and could subsequently lead to fibrosis and tissue dysfunction.
Sköld
C M
CM
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, USA.
Ohkuni
Y
Y
Liu
X D
XD
Numerof
R
R
Rennard
S I
SI
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003094:Collagen / Q000737:chemistry*; D005109:Extracellular Matrix / Q000648:ultrastructure*; D005347:Fibroblasts / Q000502:physiology*; D005355:Fibrosis / Q000473:pathology*; D005782:Gels; D006801:Humans; D006909:Hydroxyproline / Q000032:analysis; D007091:Image Processing, Computer-Assisted; D008168:Lung / Q000166:cytology / Q000196:embryology; D008407:Mast Cells / Q000201:enzymology / Q000502:physiology*; D011480:Protease Inhibitors / Q000494:pharmacology; D011487:Protein Conformation; D051381:Rats; D012697:Serine Endopeptidases / Q000494:pharmacology; D053802:Tryptases
D001562:Benzimidazoles; D005782:Gels; D011480:Protease Inhibitors; C025426:bis(5-amidino-2-benzimidazolyl)methane; D003094:Collagen; D012697:Serine Endopeptidases; C509223:Tpsab1 protein, rat; C509221:Tpsb2 protein, rat; D053802:Tryptases; D006909:Hydroxyproline