Involvement of tachykinin receptors in Clostridium perfringens beta‐toxin‐induced plasma extravasation

Abstract

1 Clostridium perfringens beta-toxin causes dermonecrosis and oedema in the dorsal skin of animals. In the present study, we investigated the mechanisms of oedema induced by the toxin. 2 The toxin induced plasma extravasation in the dorsal skin of Balb/c mice. 3 The extravasation was signi®cantly inhibited by diphenhydramine, a histamine 1 receptor antagonist. However, the toxin did not cause the release of histamine from mouse mastocytoma cells. ]-SP and spantide, inhibited the toxin-induced leakage in a dose-dependent manner. Furthermore, the non-peptide tachykinin NK 1 receptor antagonist, SR140333, markedly inhibited the toxin-induced leakage. 5 The leakage induced by the toxin was markedly reduced in capsaicin-pretreated mouse skin but the leakage was not aected by systemic pretreatment with a calcitonin gene-related peptide receptor antagonist ]-bradykinin), but was not aected by the selective L-type Ca 2+ channel blocker, verapamil, the P-type Ca 2+ channel blocker, o-agatoxin IVA, tetrodotoxin (TTX), the TTX-resistant Na + channel blocker, carbamazepine, or the sensory nerve conduction blocker, lignocaine. 7 These results suggest that plasma extravasation induced by beta-toxin in mouse skin is mediated via a mechanism involving tachykinin NK 1 receptors.

Role of Pore-Forming Toxins in Bacterial Infectious Diseases

“…The increased blood pressure can be counteracted by coadministering alpha-adrenergic and ganglionic blocking agents, indicating that ␤-toxin's effect is likely also neuronal and involves catecholamines (412). Consistently, sensory nerve-mediated mechanisms appear to be involved in ␤-toxin-induced plasma extravasation (413). C. perfringens PFO was found to reduce blood pressure and affect cardiac output, although not acting directly on the heart, thus causing lethal shock in rabbits (414).…”

“…A histamine H1 receptor antagonist markedly inhibited ␤-toxin-induced plasma extravasation. Further data, however, suggested that ␤-toxin does not act on mast cells directly, so rather than histamine release from skin mast cells, it seems that sensory nerve-mediated mechanisms are involved in plasma extravasation (413).…”

The enteric toxins of Clostridium perfringens

“…This study also reported the insertion rate of b-toxin into membranes is stimulated by the presence of divalent cations. Nagahama et al (2003) recently demonstrated the HL 60 (Human leukemia cell) cell line is also susceptible to b-toxin; in this cell culture model, b-toxin induces K + efflux and Ca 2+ , Na + and Cl -influxes, which then produce cell swelling and cell lysis.…”

The p38 MAPK and JNK Pathways Protect Host Cells against Clostridium perfringens Beta-Toxin

“…This disease is characterized by an acute sudden onset, severe hemorrhage into the lumen of the small intestine, and early death. Beta-toxin possesses lethal, dermonecrotic, plasma extravasation, and pressor activities (2)(3)(4)(5)(6).…”