Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 192, Issue 3, Pages 367-380Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.192.3.367
Keywords
kinin B(1) receptor; leukocyte-endothelial cell interaction; intravital microscopy; C fiber; mast cell
Categories
Ask authors/readers for more resources
Using intravital microscopy, we examined the role played by B(1) receptors in leukocyte trafficking across mouse mesenteric postcapillary venules in vivo. B(1) receptor blockade attenuated interleukin (IL)-1 beta-induced (5 ng intraperitoneally, 2 h) leukocyte-endothelial cell interactions and leukocyte emigration (similar to 50% reduction). The B(1) receptor agonist des-Ahr(9)bradykinin (DABK), although inactive in saline- or IL-8-treated mice: caused marked neutrophil rolling, adhesion, and emigration 23 h after challenge with IL-1 beta (when the cellular response to IL-1 beta had subsided). Reverse transcriptase polymerase chain reaction and Western blot revealed a temporal association between the DABK-induced response and upregulation of mesenteric B(1) receptor mRNA and de novo protein expression after IL-1 beta treatment. DABK-induced leukocyte trafficking was antagonized by the B(1) receptor antagonist dits-arg(10)HOE 140 but not by the B(2) receptor antagonist HOE 140. Similarly, DABK effects were maintained in B(2) receptor knockout mice. The DABK-induced responses involved the release of neuropeptides from C fibers, as capsaicin treatment inhibited the responses. Treatment with the neurokinin (NK), and NK(3) receptor antagonists attenuated the responses, whereas NK(2), calcitonin gene-related peptide, or platelet-activating factor receptor antagonists had no effect. Substance P caused leukocyte recruitment that, similar to DABK, was inhibited by NK(1) and NK(3) receptor blockade. Mast cell depletion using compound 48/80 reduced DABK-induced leukocyte trafficking, and DABK treatment was shown histologically to induce mast cell degranulation. DABK-induced trafficking was inhibited by histamine H(1) receptor blockade. Our findings provide clear evidence that B(1) receptors play an important role in the mediation of leukocyte-endothelial cell interactions in postcapillary venules, leading to leukocyte recruitment during an inflammatory response. This involves activation of C fibers and mast cells, release of substance P and histamine, and stimulation of NK(1), NK(3), and H(1) receptors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available