Roles of Mast Cells and Histamine in Mosquito Bite-Induced Allergic Itch-Associated Responses in Mice

Abstract

ABSTRACT-We investigated itch-associated responses (scratching) to mosquito bites and the role of histamine and mast cells in mosquito-induced itching in mice. Although the first bites of mosquito Aedes albopictus did not increase scratching, repeated bites increased scratching. The response was not diminished even after an interval of 2 months. Similarly, repeated intradermal (i.d.) injections of salivary gland extract (SGE) from Aedes albopictus increased scratching after SGE injection itself and mosquito bites. The scratching peaked within 10 min and almost subsided by 60 min. The opioid antagonist naloxone (1 mg / kg, s.c.) inhibited scratching following SGE injection. Although the non-sedative H 1-histamine-receptor antagonist terfenadine (30 mg/ kg, p.o.) significantly suppressed scratching induced by histamine (100 nmol /site, i.d.) in either naive or mosquito-sensitized mice, it did not affect mosquito-induced scratching in mosquitosensitized mice. Repeated injections of SGE increased scratching in mast cell-deficient (WBB6F1-W /W v ) mice as well as in normal (WBB6F1-+/ +) littermates. Repeated exposure to mosquito bites roughly doubled serum concentrations of total IgE and IgG1, but not IgG2a. Repeated injections of SGE markedly increased plasma extravasation induced by mosquito bites and such an increase was almost completely suppressed by terfenadine (30 mg/ kg, p.o.). The results show the presence of histamine-mediated and histamineindependent mechanisms in cutaneous itching and suggest that histamine probably released from mast cells does not play an important role in itching in immediate allergic reaction. Our murine model of mosquito itching may be useful for studying the mechanisms of immediate allergic itching.

Anopheles Mosquito Bites Activate Cutaneous Mast Cells Leading to a Local Inflammatory Response and Lymph Node Hyperplasia

“…Mast cells are known to induce such local reaction by rapidly releasing several mediators, including granule-associated histamine, tryptase, TNF-␣, MIP-2, as well as eicosanoids, including leukotrienes. A parallel can be made with a previous work showing that increased plasma extravasation was induced by mosquito bites in repeatedly immunized mice with Aedes albopictus salivary gland extracts (30). However, this effect was ascribed to a IgE-and IgG1-mediated specific immune response.…”

5-Hydroxytryptamine (5-HT)2Receptor Involvement in Acute 5-HT-Evoked Scratching but Not in Allergic Pruritus Induced by Dinitrofluorobenzene in Rats

“…It is of interest to compare the present results with those of a related study of scratching elicited by mosquito bites (Ohtsuka et al, 2001). In the latter study, mice were initially exposed to mosquito bites or received intradermal injection of mosquito salivary gland extract.…”

“…They were subsequently challenged with mosquito bites (or salivary gland extract) twice weekly. There was a progressive increase in the number of scratching bouts that became significant after 7 and 2 weeks, respectively, for mosquito bites and injections of salivary gland extract (Ohtsuka et al, 2001). Scratching elicited by mosquito bites was not affected by an H1 histamine an- tagonist.…”

“…However, there is as yet no effective medication for this type of pruritus. Rodent mod-els of allergic pruritus have recently been developed (Tahara et al, 1999;Inagaki et al, 2000;Ohtsuka et al, 2001;Laidlaw et al, 2002). The mouse or guinea pig is passively sensitized with a murine monoclonal IgE antibody specific for the dinitrophenyl group and is later challenged with 2,4-dinitrofluorobenzene (DNFB) (Tahara et al, 1999;Inagaki et al, 2000) or repeated epicutaneous application of dinitrochlorobenzene (Laidlaw et al, 2002).…”

Itch-Associated Response Induced by Experimental Dry Skin in Mice

“…Naloxone suppresses experimental itch induced by histamine in humans (29). With regard to animals, opioid antagonists inhibit scratching elicited by intradermal injection of pruritogens such as substance P and serotonin (20,22) and scratching following the immediate allergic response (24). Spontaneous scratching in mice with chronic dermatitis is also suppressed by opioid antagonists (21).…”