Histamine Induces Vascular Hyperpermeability by Increasing Blood Flow and Endothelial Barrier Disruption In Vivo

Ashina, Kohei; Tsubosaka, Yoshiki; Nakamura, Tatsuro; Omori, Keisuke; Kobayashi, Koji; Hori, Masaru; Ozaki, Hiroshi; Murata, Takahisa

doi:10.1371/journal.pone.0132367

Cited by 161 publications

(148 citation statements)

References 27 publications

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“…Phosphorylation of VE-cadherin by tyrosine is a general mechanism involved in weakening of the endothelial cell barrier resulting from cell stimulation. It is likely that histamine and bradykinin, the 2 main mediators involved in angioedema, exert their permeabilizing effect mainly through phosphorylation of VE-cadherin [7,8]. Detection of soluble VE-cadherin in the serum of patients with a form of primary angioedema during an attack reinforces this view [9].…”

Section: Pathophysiologymentioning

confidence: 89%

“…The 2 major factors that determine vascular permeability are blood flow and endothelial barrier function [10]. In the case of histamine, a recent study revealed that hyperpermeability is due mainly to the NO-induced increase in blood flow, which in turn is controlled by stimulation by vascular endothelial growth factor [7,11]. According to this finding, rubor and calor are features of histaminergic urticaria and tend to be more evident in histaminergic forms of angioedema than in nonhistaminergic forms.…”

Section: Pathophysiologymentioning

confidence: 99%

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Novelties in the Diagnosis and Treatment of Angioedema

Cicardi¹,

Suffritti²,

Perego³

et al. 2016

J Investig Allergol Clin Immunol

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Angioedema is defined as local, noninflammatory, self-limiting edema that is circumscribed owing to increased leakage of plasma from the capillaries located in the deep layers of the skin and the mucosae. Two mediators, histamine and bradykinin, account for most cases of angioedema. Angioedema can occur with wheals as a manifestation of urticaria, and this form is frequently allergic. In the present review, we discuss nonallergic angioedema without wheals, which can be divided into 3 acquired and 4 hereditary forms. Histamine is the mediator in acquired angioedema of unknown etiology (idiopathic histaminergic acquired angioedema), whereas in other forms the main mediator is bradykinin. Angioedema can be caused by C1-inhibitor deficiency (C1-INH-hereditary angioedema and C1-INH-acquired angioedema), mutations in coagulation factor XII (FXII-hereditary angioedema), and treatment with angiotensin-converting enzyme inhibitors (ACEI-acquired angioedema). Etiology remains unclear in acquired angioedema (idiopathic nonhistaminergic acquired angioedema) and in 1 type of hereditary angioedema (hereditary angioedema of unknown origin). Several treatments are licensed for hereditary C1-INH deficiency. Plasma-derived and recombinant C1-INHs, the bradykinin receptor blocker icatibant, and the plasma kallikrein inhibitor ecallantide have been approved for on-demand treatment to reverse angioedema symptoms. Attenuated androgen and plasma-derived C1-INH are approved for prophylaxis. Key words: Angioedema. Bradykinin. Histamine. C1 inhibitor. Coagulation factor XII. Angiotensin-converting enzyme inhibitors. Urticaria. ResumenAngioedema se define como un edema local, autolimitado, no-inflamatorio. Se trata de un edema circunscrito debido a la trasvasación de plasma de los capilares localizados en los sustratos profundos de la piel y de las mucosas. En la mayoría de los casos están implicados dos mediadores, la histamina y la serotonina. Puede manifestarse en forma de habones como en la urticaria de origen alérgico. El angioedema de origen no alérgico es el motivo de esta revisión. Se puede presentar bajo 3 formas adquiridas y 4 formas hereditarias. La histamina es el mediador implicado en el angioedema adquirido de etiología desconocida (angioedema adquirido idiopático histaminérgico). En las otras formas se sospecha que es la serotonina el mediador principal. La etiología del angioedema puede ser identificado en 4 tipos: una deficiencia de C1-inhibidor (C1-INH-angioedema hereditario y C1-INH-angioedema adquirido), mutaciones en el factor XII de coagulación (FXII-angioedema hereditario), tratamiento con inhibidores del enzima convertidor de la angiotensina (ACEi-angioedema adquirido). En uno de los adquiridos (angioedema adquirido idiopático no histaminérgico) y en el hereditario de origen desconocido, no se ha identificado todavía su etiología. Varios tratamientos están aprobados para revertir los síntomas clínicos y se aplican en la deficiencia de angioedema hereditario por déficit de C1-INH: Derivados de plasma y C1-IN...

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Section: Pathophysiologymentioning

confidence: 89%

Section: Pathophysiologymentioning

confidence: 99%

Novelties in the Diagnosis and Treatment of Angioedema

Cicardi¹,

Suffritti²,

Perego³

et al. 2016

J Investig Allergol Clin Immunol

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“…However, the exact contribution of various segments of the tumour neovasculature to permeability remains poorly understood. In addition to an arsenal of inflammatory mediators such as histamine 106,107 , the interaction of tight junction modulators such as cationic polymers with endothelium can also induce endothelial contraction and tight junction disassembly, leading to vascular leakiness 108 . For tumours, both vascular permeability and blood velocity are complex and kinetically variable from segment to segment 109 .…”

Section: Enhancing Drug Delivery To the Tumourmentioning

confidence: 99%

Cancer nanomedicine: progress, challenges and opportunities

et al. 2016

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The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a new paradigm in cancer therapy stem from the complexities and heterogeneity of tumour biology, an incomplete understanding of nano–bio interactions and the challenges regarding chemistry, manufacturing and controls required for clinical translation and commercialization. This Review highlights the progress, challenges and opportunities in cancer nanomedicine and discusses novel engineering approaches that capitalize on our growing understanding of tumour biology and nano–bio interactions to develop more effective nanotherapeutics for cancer patients.

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“…Our results demonstrate that BaP1 is able to disrupt the endothelial barrier in PCV in the in vivo model. This change in the morphology induced by BaP1 in cell-cell junctions is similar to that described after an inflammatory stimulus, and is associated with changes in VE-cadherin localization, internalization or disassembly [47–49]. Interestingly, a mechanism of SVMP-induced extravasation, known as haemorrhage per diapedesis , has been described in PCV; in this case erythrocyte extravasation occurs through widened intercellular junctions in venular endothelial cells [11].…”

Section: Discussionmentioning

confidence: 59%

Effects of PI and PIII Snake Venom Haemorrhagic Metalloproteinases on the Microvasculature: A Confocal Microscopy Study on the Mouse Cremaster Muscle

et al. 2016

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The precise mechanisms by which Snake Venom Metalloproteinases (SVMPs) disrupt the microvasculature and cause haemorrhage have not been completely elucidated, and novel in vivo models are needed. In the present study, we compared the effects induced by BaP1, a PI SVMP isolated from Bothrops asper venom, and CsH1, a PIII SVMP from Crotalus simus venom, on cremaster muscle microvasculature by topical application of the toxins on isolated tissue (i.e., ex vivo model), and by intra-scrotal administration of the toxins (i.e., in vivo model). The whole tissue was fixed and immunostained to visualize the three components of blood vessels by confocal microscopy. In the ex vivo model, BaP1 was able to degrade type IV collagen and laminin from the BM of microvessels. Moreover, both SVMPs degraded type IV collagen from the BM in capillaries to a higher extent than in PCV and arterioles. CsH1 had a stronger effect on type IV collagen than BaP1. In the in vivo model, the effect of BaP1 on type IV collagen was widespread to the BM of arterioles and PCV. On the other hand, BaP1 was able to disrupt the endothelial barrier in PCV and to increase vascular permeability. Moreover, this toxin increased the size of gaps between pericytes in PCV and created new gaps between smooth muscle cells in arterioles in ex vivo conditions. These effects were not observed in the case of CsH1. In conclusion, our findings demonstrate that both SVMPs degrade type IV collagen from the BM in capillaries in vivo. Moreover, while the action of CsH1 is more directed to the BM of microvessels, the effects of BaP1 are widespread to other microvascular components. This study provides new insights in the mechanism of haemorrhage and other pathological effects induced by these toxins.

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Histamine Induces Vascular Hyperpermeability by Increasing Blood Flow and Endothelial Barrier Disruption In Vivo

Cited by 161 publications

References 27 publications

Novelties in the Diagnosis and Treatment of Angioedema

Novelties in the Diagnosis and Treatment of Angioedema

Cancer nanomedicine: progress, challenges and opportunities

Effects of PI and PIII Snake Venom Haemorrhagic Metalloproteinases on the Microvasculature: A Confocal Microscopy Study on the Mouse Cremaster Muscle

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