Contribution of B₂ receptors for bradykinin in Arthus reaction‐induced plasma extravasation in wild‐type or B₂ transgenic knockout mice

Abstract

1 The aim of the present study was to investigate the contribution of bradykinin (BK) B 1 and B 2 receptors in a model of type III hypersensitivity, the reverse passive Arthus reaction (RPA), in wildtype mice and transgenic B 2 knockout littermates. 2 BK (10 mg mouse 71 ) or bovine serum albumin (0.5 mg mouse 71 ) induced a sustained Evans blue extravasation for more than 80 min in naive or rabbit anti-bovine serum albumin-treated mice (RPA model), respectively. The response to the two stimuli was prevented by the B 2 receptor antagonist, HOE-140, but not by [Leu 8 ]desArg 9 -BK (B 1 receptor antagonist). 3 In contrast to the wild-type littermates, RPA and bradykinin were unable to trigger an increase in plasma extravasation in B 2 knockout mice. 4 Furthermore, endothelin-1 (5 mg mouse 71 ) and a selective NK-1 receptor agonist [Sar 9 ,Met (O 2 ) 11 ]-SP (20 mg mouse 71 ), triggered a signi®cant increase in peritoneal plasma extravasation in both wild-type and B 2 knockout animals. 5 A pretreatment with indomethacin (200 mg mouse 71 ) signi®cantly reduced the RPA-induced but not the BK-induced increase in Evans blue extravasation. Furthermore, RPA, but not BK, triggered a signi®cant indomethacin-sensitive increase in peritoneal prostaglandin E 2 content. 6 Our results suggest a pivotal role for B 2 receptors in the mechanism of plasma extravasation which occurs during the reverse passive Arthus reaction in the mouse. Moreover, our results suggest an important contribution of prostanoids in the plasma leakage mechanisms triggered by RPA but not by bradykinin.

Immune complex-mediated tissue injury: a multistep paradigm

“…Factor XII initiates the activation of the kinin cascade, thereby leading to bradykinin generation. Bradykinin exerts a modulatory effect on IC pneumonitis in mice, because blockade of the bradykinin B 2 receptor increases PMN infiltration but not their activation nor the hemorrhagic lesion [56] and also reduces plasma leakage [36]. The difficulty in demonstrating the activation of the coagulation cascade in IC-mediated lesions is best explained by the increased activity of the fibrinolytic system triggered by tissue-type plasminogen activator released from mast cells [57] and endothelium [58] in response to the inflammatory mediators generated under these conditions.…”

“…Intravital fluorescence microscopy techniques have enabled the visualization of antigen slowly diffusing into the perivenular sites in naïve animals, whereas in sensitized animals, antigen leakage enables IC formation and a rapid extravasation of plasma [30] mediated by PAF [31] and other mediators released from both perivascular macrophages and mast cells upon FcgR crosslinking [32][33][34]. Both C5a anaphylatoxin [35] and bradykinin [36] contribute to plasma leakage as well. Massive influx of PMNs and hemorrhagic lesions occur after 24 hours [37], as it happens, for instance, in the lungs and skin, whereas degradation of proteoglycans is observed in joints [37].…”

Modulation of allergic and immune complex-induced lung inflammation by bradykinin receptor antagonists

“…However, the role of bradykinin receptors in this type of lung inflammation was never investigated. In immune complex-induced inflammation in the peritoneal cavity, bradykinin has an important role in the mechanism of plasma extravasation and this action seems to be mediated directly by bradykinin B 2 receptors [16].…”

International Union of Pharmacology. XLV. Classification of the Kinin Receptor Family: from Molecular Mechanisms to Pathophysiological Consequences

“…Thus, specific B 2 receptor antagonists or inactivation of the B 2 receptor in knockout mice prevent specific aspects of the inflammatory response in specific models, e.g., tissue swelling and systemic signs of inflammation in peptidoglycan-induced arthritis in the Lewis rat (Uknis et al, 2001) and plasma extravasation in the Arthus reaction (Samadfam et al, 2000). B 2 receptor antagonism may have a special interest in some forms of vasogenic edema, the brain edema that follows head trauma or stroke and hereditary angioedema.…”