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Different interaction of mast cells with human endothelial cells and fibroblasts
1Department of Dermatology, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, 321-0293 Tochigi, Japan. tohtsuka@dokkyomed.ac.jp
Abstract:
In a number of chronic inflammatory conditions resulting in fibrosis, perivascular mononuclear cell infiltration including mast cells (MC) has been shown before the onset of vascular injury and interstitial fibrosis. These observations suggest a role for MC in inducing endothelial cell (EC) injury and fibroblast (FB) proliferation and collagen synthesis. In view of these observations, the interactions of MC with EC and FB were studied. MC adhesion to EC and FB showed time-dependent increase reaching a plateau at 1 and 3 hrs, respectively. With added MC, the proliferation of EC showed a dose-dependent decrease, but that of FB, a dose-dependent increase. MC, MC surpernatant and sonicated MC induced dose-dependent cytotoxic activity to EC, whose cytotoxicy was inhibited by trypsin inhibitor. FB cocultured with MC showed 9.95 times collagen synthesis and 11.0 times protein synthesis compared with FB without MC. These results showed that 1) MC attached to EC inhibited the proliferation by cytotoxic activity to EC, which was due to a kind of proteolytic enzyme involving trypsin, 2) MC had proliferative and collagen synthetic activity to FB. These results suggest the possibility that MC have a role in a number of chronic inflammatory diseases resulting in vascular injury and interstitial fibrosis.
Insights
Mast cells (MC) interact with endothelial cells (EC) and fibroblasts (FB) in chronic inflammation. MC inhibit EC proliferation and promote FB collagen synthesis, suggesting a role in fibrosis and vascular injury.
Area of Science:
- Immunology
- Cell Biology
- Pathology
Background:
- Chronic inflammatory conditions often involve fibrosis, perivascular mononuclear cell infiltration, and vascular injury.
- Mast cells (MC) are implicated in initiating endothelial cell (EC) injury and fibroblast (FB) proliferation, leading to fibrosis.
Purpose of the Study:
- To investigate the interactions between mast cells (MC), endothelial cells (EC), and fibroblasts (FB).
- To elucidate the role of MC in EC injury and FB proliferation and collagen synthesis.
Main Methods:
- Assessed MC adhesion to EC and FB over time.
- Quantified EC and FB proliferation in the presence of MC.
- Evaluated the cytotoxic effects of MC on EC, with and without trypsin inhibitor.
- Measured collagen and protein synthesis in FB co-cultured with MC.
Main Results:
- MC adhesion to EC and FB increased over time.
- MC inhibited EC proliferation but stimulated FB proliferation in a dose-dependent manner.
- MC exhibited dose-dependent cytotoxic activity towards EC, mediated by a trypsin-like enzyme.
- MC co-culture significantly increased FB collagen and protein synthesis.
Conclusions:
- Mast cells (MC) can inhibit endothelial cell (EC) proliferation through cytotoxic mechanisms involving proteolytic enzymes.
- Mast cells (MC) promote fibroblast (FB) proliferation and collagen synthesis.
- These findings suggest a significant role for MC in the pathogenesis of chronic inflammatory diseases characterized by vascular injury and fibrosis.