Histamine modulates mast cell degranulation through an indirect mechanism in a model IgE‐mediated reaction

Abstract

Histamine is released in inflammatory reactions and exerts an immunoregulatory function on cells present in the microenvironment. In this study, we compared the effect of histamine on degranulation of mast cells derived from animals bearing a parasitic infection with those from uninfected animals. Peritoneal mast cells (PMC) were obtained 24 days after infection of Wistar rats with Toxocara canis. The degree of degranulation was assessed either morphologically or by measuring the release of β‐hexosaminidase and TNF‐α. Non‐purified PMC or mast cells immunomagnetically purified with mAb AA4 were used. An increase in degranulation of non‐purified mast cells from infected animals was observed after incubation with histamine in vitro or when histamine was injected into the peritoneal cavity. When a purified mast cell population was used, this effect was no longer observed. Supernatants from spleen cells stimulated with histamine induced degranulation of purified mast cells, and again, this was potentiated with PMC from infected animals. However, when supernatants from peritoneal macrophages similarly stimulated were used, a reduction in the degranulation of PMC from infected animals was observed. Our results suggest that histamine may act as a regulator of mast cell degranulation, thus modulating inflammatory responses due to infection with certain parasites.

Evidence for eosinophil recruitment, leukotriene B4 production and mast cell hyperplasia following Toxocara canis infection in rats

“…Another study also demonstrated a role for endogenous stem cell factor production in mediating eosinophil recruitment in an allergic pleurisy model in mice (35). Moreover, the authors also showed that the effects of stem cell factor were dependent on the release of LTB 4 , which was most likely produced by mast cells.…”

“…The production of LTB 4 was assessed in the serum of T. canis-infected rats and -uninfected rats that received only saline (control). Levels of LTB 4 in the serum from T. canisinfected rats were significantly higher on the 3rd, 18th, and 24th days after infection compared to control rats.…”

Evidence for eosinophil recruitment, leukotriene B4 production and mast cell hyperplasia following Toxocara canis infection in rats

“…In brief, the cell suspensions were recovered and centrifuged, and the cells were exposed to Tris-NH 4 microplates were then centrifuged at 200 g at 4°C for 10 min. The supernatants were carefully removed, 100 µL substrate solution (2.4 mM o-phenylenediamine dihydrochloride in 50 mM Tris-HCl, pH 8.0, with 6.6 mM H 2 O 2 ) was added to each well, and the plates were incubated at room temperature for 15 min.…”

“…In general, helminthic parasites infect vertebrate hosts and typically promote a Th2-type inflammatory response that is marked by eosinophilia, high levels of immunoglobulin E (IgE) and mast cell hyperplasia (2). Studies from our laboratory have shown an accumulation of eosinophils and increased total serum IgE during the course of T. canis infection in guinea pigs (3) and Wistar rats (4). Despite the presence of elevated levels of circulating IgE during eosinophilic inflammation (5,6) and the capacity of mast cell secretory products to promote the traffic of leukocytes to the challenge sites (7,8), the relative importance of the IgE-mast cell system for the maintenance of the chronic inflammatory response to helminthic infections is controversial.…”

“…It has been shown that IgE-driven inflammation may lead to eosinophil accumulation through a mechanism dependent on eotaxin, platelet-activating factor and LTs (17). Moreover, it has been shown that eosinophil migration to the rat peritoneal cavity is mediated by mast cells, which release chemotactic factors such as LTB 4 after stimulation (18).…”