Heme Oxygenase/Carbon Monoxide-biliverdin Pathway Down Regulates Neutrophil Rolling, Adhesion and Migration in Acute Inflammation.
From: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
British journal of pharmacology
- Publish Date: Oct 2006
- ISSN: 0007-1188
- Volume: 149
- Issue: 4
- Pages: 345-54
- Medium: Print
- Language: English
- Citation (JAMA): Freitas A, Alves-Filho J C, Secco D D, et al. Heme Oxygenase/Carbon Monoxide-biliverdin Pathway Down Regulates Neutrophil Rolling, Adhesion and Migration in Acute Inflammation.. Br. J. Pharmacol. Oct 2006;149:345-54
Abstract
BACKGROUND AND PURPOSE: Heme oxygenase (HO) activity is known to down-regulate inflammatory events. Here, we address the role of HO and its metabolites, carbon monoxide (CO) and biliverdin (BVD), in leukocyte rolling, adhesion and neutrophil migration during inflammatory processes. EXPERIMENTAL APPROACH: Intravital microscopy was used to evaluate leukocyte rolling and adhesion in the mesenteric microcirculation of mice. TNFalpha and IL-1beta were determined by ELISA and HO-1 protein expression by Western blot. KEY RESULTS: Intraperitoneal challenge with carrageenan enhanced HO-1 protein expression in mesentery and bilirubin concentration in peritoneal exudates. Pretreatment of mice with a non-specific inhibitor of HO (ZnDPBG) or with a HO-1 specific inhibitor (ZnPP IX) enhanced neutrophil migration, rolling and adhesion on endothelium induced by carrageenan. In contrast, HO substrate (hemin), CO donor (DMDC) or BVD reduced these parameters. The reduction of neutrophil recruitment promoted by HO metabolites was independent of the production of chemotactic cytokines. Inhibitory effects of CO, but not of BVD, were counteracted by treatment with a soluble guanylate cyclase (sGC) inhibitor, ODQ. Furthermore, inhibition of HO prevented the inhibitory effect of a nitric oxide (NO) donor (SNAP) upon neutrophil migration, while the blockade of NO synthase (NOS) activity by aminoguanidine did not affect the CO or BVD effects. CONCLUSIONS AND IMPLICATIONS: Metabolites of HO decreased leukocyte rolling, adhesion and neutrophil migration to the inflammatory site by a mechanism partially dependent on sGC. Moreover, inhibition by NO of neutrophil migration was dependent on HO activity.
Mesh Headings (Keywords): Animals, Biliverdine, Carbon Monoxide, Carrageenan, Cell Adhesion, Cell Movement, Deuteroporphyrins, Dose-Response Relationship, Drug, Enzyme Inhibitors, Guanylate Cyclase, Heme Oxygenase (Decyclizing), Hemin, Inflammation, Interleukin-1beta, Leukocyte Rolling, Mesenteric Veins, Mice, Mice, Inbred BALB C, Microscopy, Video, Neutrophils, Nitric Oxide, Protoporphyrins, Receptors, Cytoplasmic and Nuclear, Tumor Necrosis Factor-alpha
Check for Full Text / PubMed Unique Identifier (PMID): 16953189
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