Effect of a kinin B₂ receptor antagonist on LPS‐ and cytokine‐induced neutrophil migration in rats

Abstract

1 This study examines the involvement of kinins in neutrophil migration into rat subcutaneous air pouches triggered by lipopolysaccharide (LPS), as well as the putative roles played by kinin B 1 and B 2 receptors, tumour necrosis factor alpha (TNF-a), interleukin-1 beta (IL-1b) and selectins in this response. 2 LPS (5 ng to 10 mg cavity À1 ) injected into the 6-day-old pouch induced a dose-and time-dependent neutrophil migration which peaked between 4 and 6 h, and was maximal following the dose of 100 ng cavity À1 (saline: 0.4670.1; LPS: 4373.70 Â 10 6 cells cavity À1 at 6 h). 3 Bradykinin (BK) (600 nmol) injected into the pouch of saline-treated rats induced only modest neutrophil migration (0.7370.16 Â 10 6 cells cavity À1 ). A more robust response to BK (3.270.25 Â 10 6 cells cavity À1 ) was seen in animals pretreated with captopril, but this was still smaller than the responses to IL-1b or TNF-a (15 pmol: 2372.2 Â 10 6 and 75 pmol: 29.572 Â 10 6 cells cavity À1 , respectively). Nevertheless, the B 1 agonist des-Arg 9 -BK (600 nmol) failed to induce neutrophil migration. 4 HOE-140 (1 and 2 mg kg À1 ), a B 2 receptor antagonist, reduced LPS-induced neutrophil migration. HOE-140 also reduced the neutrophil migration induced by BK, but had no effect on the migration promoted by IL-1b or TNF-a. des-Arg 9 -[Leu 8 ]-BK, B 1 receptor antagonist was ineffective in changing neutrophil migration caused by any of these stimuli. 5 Neutrophil migration induced by LPS or BK was reduced by interleukin-1 receptor antagonist (IL1ra) (1 mg kg À1 ), sheep anti-rat TNF serum (anti-TNF serum) (0.3 ml cavity À1 ), and the nonspecific selectin inhibitor fucoidin (10 mg kg À1 ). 6 TNF-a levels in the pouch fluid were increased by LPS or BK injection, peaking at 0.5 -1 h and gradually declining thereafter up to 6 h. IL-1b levels increased steadily throughout the 6 h period. HOE-140 markedly inhibited the rise in IL-1b and TNF-a levels in pouch fluid triggered by both stimuli. 7 These results indicate that BK participates importantly in selectin-dependent neutrophil migration into the air pouch triggered by LPS in the rat, by stimulating B 2 receptors coupled to synthesis/release of TNF-a and IL-1b.

Inhibitory effect ofCareya arboreaon inflammatory biomarkers in carrageenan-induced inflammation

“…substance P (Kuo et al, 2000;Santos et al, 2003). CAME was more effective in suppressing the serum level of TNF-a than indomethacin.…”

Endogenous Bradykinin Contributes to Increased Plasminogen Activator Inhibitor 1 Antigen following Hemodialysis

“…Thus, bradykinin stimulates lung fibroblasts, type II alveolar cells, macrophages, and bronchial epithelial cells to release inflammatory cytokines and chemotactic factors such as MCP-1, whereas B 2 receptor antagonism decreases cytokine-induced neutrophil migration. 16,43 On the basis of these data, ACE inhibitors, which potentiate bradykinin, could have a proinflammatory effect during hemodialysis.…”

“…[12][13][14] On the other hand, bradykinin also stimulates activation of nuclear factor B and cytokine expression via the B 2 receptor. 15,16 Understanding the contribution of endogenous bradykinin to the inflammatory response to hemodialysis has important implications for the prevention of atherothrombotic events.…”

β2-Adrenergic receptor-dependent sexual dimorphism for murine leukocyte migration

“…Four hours after injection, mice were euthanized and their air pouches washed three times with 1 ml sterile phosphate buffered saline (PBS). This time point was chosen since we are interested in the neutrophil component of the early inflammatory response and neutrophil recruitment into the air pouch is maximal around four hours after LPS (Santos et al, 2003). The lavage exudates were centrifuged, cell pellets, containing ~1×10 6 cells, resuspended in 1 ml of PBS + 1% BSA + 1 μg/ml propidium iodide + 5 μg/ml Hoechst-33342 and viable cells counted by flow cytometry using a dual-laser FACStar cell sorter (Becton Dickinson, San Jose, CA).…”