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Evidence of mast-cell histamine being mitogenic in intact tissue
Abstract:
We have reported previously that secretion by connective tissue mast cells (MCs) causes mitogenesis in adjacent cells in diverse rat tissues. In cultured rat mesentery there was a spontaneous release of about 45% of the histamine in 2 days, and a spontaneous marked increase in basal proliferation of the mesentery. The MC secretagogues, compound 48/80 and polymyxin B, released additional histamine and stimulated mitogenesis further. In contrast, 48/80 added to cultures of guinea-pig mesentery, the MC of which are unresponsive to the drug, did not affect the basal proliferation. However, exogenous histamine at 10(-10) M mitogenically stimulated the cultured guinea-pig mesentery. A histamine H2-receptor antagonist, which itself was mitogenically inert, significantly suppressed the 48/80-induced MC-mediated mitogenesis in rat mesentery in vivo and in vitro. On the other hand, a histamine H1-receptor antagonist did not affect this MC-mediated mitogenesis in rat. Our findings indicate that histamine is one of possibly several mitogens which are released or activated by the secreting MC.
Insights
Connective tissue mast cells (MCs) release histamine, promoting cell proliferation (mitogenesis). Histamine acts as a key mitogen, with its effects mediated through H2 receptors, influencing cell growth in rat tissues.
Area of Science:
- Cell Biology
- Immunology
- Histamine Signaling
Background:
- Connective tissue mast cells (MCs) are known to influence adjacent cells through secreted factors.
- Previous work indicated MC secretion can induce mitogenesis in various rat tissues.
Purpose of the Study:
- To investigate the role of mast cell (MC) secretion in stimulating cell proliferation (mitogenesis).
- To identify the specific mediators involved in MC-driven mitogenesis, particularly histamine.
Main Methods:
- Culturing rat and guinea-pig mesentery tissues.
- Stimulating MCs with secretagogues (compound 48/80, polymyxin B).
- Assessing histamine release and cell proliferation.
- Utilizing histamine receptor antagonists (H1 and H2) to block specific pathways.
Main Results:
- Spontaneous histamine release and increased proliferation observed in cultured rat mesentery.
- MC secretagogues enhanced histamine release and mitogenesis in rats, but not in guinea-pigs.
- Exogenous histamine induced mitogenesis in guinea-pig mesentery.
- A histamine H2-receptor antagonist suppressed MC-mediated mitogenesis in rats, while an H1 antagonist had no effect.
Conclusions:
- Histamine is a significant mitogen released by secreting mast cells (MCs).
- MC-mediated mitogenesis in rats involves histamine acting via H2 receptors.
- These findings highlight histamine's role in regulating cell proliferation through mast cell activation.