Mast Cell Degranulation Alters Lymphatic Contractile Activity Through Action of Histamine

Abstract

Objective: Mast cells reside in most tissues and in close association with blood vessels and nerves, areas where lymphatic vessels are also present. Mast cells and lymphatic vessels are two important players in the development of the inflammatory process. This study was designed to examine the effects of mast cell degranulation on the contractile activity of mesenteric lymphatic vessels.

Methods: Lymphatic vessel contractile activity was assessed in vitro by video microscopy of the mesentery of cow's milk-sensitized guinea pigs upon application of β-lactoglobulin and compared to the response measured in sham animals.

Results: Application of 5–10 μM β-lactoglobulin increased lymphatic vessel constriction frequency and decreased constriction amplitude (n = 12). This effect was not seen in sham-treated animals (n = 16) and was not due to an increased number of mast cells in the mesentery of the milk-sensitized animals, as revealed by histological examination. Two known mast cell-derived mediators, histamine and thromboxane A₂, via stable mimetic U46619 also altered lymphatic pumping in a similar manner, but only pretreatment with the histamine H₁ receptor antagonist pyrilamine (1 μM) could reduce the β-lactoglobulin-induced response. The thromboxane A₂ receptor antagonist, SQ 29548, and the 5-lipoxygenase inhibitor, caffeic acid, were without significant effect.

Conclusion: In the in vitro mesenteric preparation, mast cell degranulation altered lymphatic contractile activity via the release of a mediator suggested to be histamine and the subsequent activation of H₁ receptors. This action could potentially interfere with the expected ability of lymphatic vessels to reduce edema during inflammation.

Key words:

• β-lactoglobulin
• inflammation
• lymphatic vessel
• video-microscopy

This study was supported by grants from the Crohn's and Colitis Foundation of Canada and the Heart and Stroke Foundation of Alberta, NWT, and Nunavut. PYvdW is an Alberta Heritage Foundation for Medical Research Scholar. The authors thank Simon Roizes, Caroline Schwab, and Martin Bratschi for excellent technical assistance; Ian Rainey for his advice related to data analysis; and Wallace MacNaughton for his valuable comments on the manuscript.