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Mast cell activation induces P-selectin-dependent leukocyte rolling and adhesion in postcapillary venules in vivo
H Thorlacius1, J Raud, S Rosengren-Beezley
1Department of Physiology & Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Abstract:
As studied by intravital microscopy, local challenge with the mast cell secretagogue compound 48/80 was found to increase the leukocyte rolling fraction, decrease rolling velocity and induce firm leukocyte adhesion in postcapillary venules of the rat mesentery. These effects of compound 48/80 were inhibited by a monoclonal anti-P-selectin antibody, but not by combined treatment with H1 and H2 histamine-receptor antagonists. Moreover, the response to compound 48/80 was not mimicked by exogenous histamine or 5-hydroxytryptamine (5-HT). These novel findings indicate that mediator(s) other than histamine and 5-HT evoke P-selectin-dependent leukocyte rolling and thereby promote firm leukocyte adhesion in mast cell-dependent inflammation.
Insights
Mast cells trigger inflammation by releasing mediators that cause leukocyte rolling and adhesion. These effects are P-selectin dependent and not mediated by histamine or serotonin.
Area of Science:
- Immunology
- Inflammation research
- Vascular biology
Background:
- Mast cells play a crucial role in inflammatory responses.
- Leukocyte adhesion to the endothelium is a key event in inflammation.
Purpose of the Study:
- To investigate the mechanisms by which mast cell secretagogues induce leukocyte adhesion.
- To identify the specific mediators involved in mast cell-dependent inflammation.
Main Methods:
- Intravital microscopy was used to study leukocyte behavior in rat mesenteric venules.
- Compound 48/80, an anti-P-selectin antibody, and histamine receptor antagonists were employed.
Main Results:
- Compound 48/80 increased leukocyte rolling and firm adhesion, mediated by P-selectin.
- Histamine and serotonin did not replicate these effects.
- Inhibition of P-selectin blocked compound 48/80-induced leukocyte adhesion.
Conclusions:
- Mast cell activation releases mediators, distinct from histamine and serotonin, that induce P-selectin-dependent leukocyte rolling and adhesion.
- These findings elucidate novel pathways in mast cell-dependent inflammatory processes.