Increase in Intradermal Vascular Permeability Caused by Pertussis Toxin from Bordetella pertussis

Abstract

Rabbits that were injected intradermally with pertussis toxin (PT), produced from Bordetella pertussis, showed slight edema and erythema at the injection sites, but not hemorrhage nor necrosis. The edema lesions were stained blue by the intravenous injection of Pontamine Sky Blue 6B dye, suggesting that PT caused increased vascular permeability, similarly to the permeability factor (PF) of cholera toxin. The reaction of the PF of PT could be determined by measuring the diameter of the blue area. The diameter of the blue area bore a good linear relationship to the logarithm of the dose of PT. The activity of the PF was neutralized by anti-PT rabbit serum. Detoxification of PT with formalin did not increase the vascular permeability, but reverted pertussis toxoid showed a PF reaction in proportion to the reverted leukocytosis-promoting and histamine-sensitizing activities of PT. The supernate of a Bordetella pertussis culture also induced a PF reaction and the reaction could be made clear by heating the supernate at 56 C for 30 min, but the supernate of Bordetella bronchiseptica did not induce the reaction at all.Pertussis toxin (PT) also called leukocytosis-promoting factor (8), histaminesensitizing factor (11), islet-activating protein (16), or pertussigen (1), is a protein toxin produced by Bordetella pertussis. It elicits various biological effects in mammals, and is shown to be an important protective antigen for mice against both intracerebral (10) and aerosol challenges (12) with virulent Bordetella pertussis.Recently we found that PT increases the vascular permeability of skin capillaries similarly to the permeability factor (PF) of cholera toxin (CT) (4) and the PF of PT shows a good correlation with the dose of PT. Munoz et al (9) reported that vascular permeability in the striated muscle of mice is increased by injecting PT intravenously (iv) ; however the PF of PT was not studied. Therefore, we examined histological changes in the skin tissues at the PT injection sites and showed that the PF reaction is one of the biological activities of PT.A variety of methods for assaying PT are known (6,8,11,16), but some problems, such as lack of simplicity, inaccuracy, and high cost remain. We found that the use of PF of PT is a simple and accurate method to determine the biological activity of PT.

Edema as a new predominant symptom of Bordetella pertussis infection in a newborn

“…Ptx activates cAMP and by this action possibly changes concentrations of protein kinase C and manganese superoxide dismutase, causing lungedema [4,15]. Ptx also can change the vascular permeability of vessels outside the lungs [12]. A second important toxin, produced by B. pertussis is an adenylate cyclase toxin (ACT), also activating cAMP.…”

In Vivo Models and In Vitro Assays for the Assessment of Pertussis Toxin Activity

“…Although these in vivo models are only suitable for specific purposes, they provide important insight into certain properties of the toxin. As discussed above, PTx affects in vivo vascular permeability, a feature which has been visualized by a model developed by Sukuma et al [ 51 ]. In this model, extravasation is monitored by intracutaneous injection of PTx combined with an intravenous administration of a blue dye in either rabbits or guinea pigs.…”

Angioedema as a predominant symptom ofBordetella pertussisinfection

“…11 It has also been shown to increase vascular permeability and thereby induce oedema. 12 Pertussis toxin results in vasodilatation by reducing the contractile properties of smooth muscle cells in resistance arteries, leading to oedema. 13 Pertussis toxin is also responsible for lymphocytosis, which was another systemic response to B. pertussis infection seen in our patient.…”