Tissue heme oxygenase-1 exerts anti-inflammatory effects on LPS-induced pulmonary inflammation
Konrad FM, Knausberg U, Hoene R, Ngamsri KC, Reutershan J (2016)
Publication Type: Journal article
Publication year: 2016
Journal
Book Volume: 9
Pages Range: 98-111
Journal Issue: 1
DOI: 10.1038/mi.2015.39
Abstract
Heme oxygenase-1 (HO-1) has been shown to display anti-inflammatory properties in models of acute pulmonary inflammation. For the first time, we investigated the role of leukocytic HO-1 using a model of HO-1 flox/flox mice lacking leukocytic HO-1 that were subjected to lipopolysaccharide (LPS)-induced acute pulmonary inflammation. Immunohistology and flow cytometry demonstrated that activation of HO-1 using hemin decreased migration of polymorphonuclear leukocytes (PMNs) to the lung interstitium and bronchoalveolar lavage (BAL) in the wild-type and, surprisingly, also in HO-1 flox/flox mice, emphasizing the anti-inflammatory potential of nonmyeloid HO-1. Nevertheless, hemin reduced the CXCL1, CXCL2/3, tumor necrosis factor-α (TNFα), and interleukin 6 (IL6) levels in both animal strains. Microvascular permeability was attenuated by hemin in wild-type and HO-1 flox/flox mice, indicating a crucial role of non-myeloid HO-1 in endothelial integrity. The determination of the activity of HO-1 in mouse lungs revealed no compensatory increase in the HO-1 flox/flox mice. Topical administration of hemin via inhalation reduced the dose required to attenuate PMN migration and microvascular permeability by a factor of 40, emphasizing its clinical potential. In addition, HO-1 stimulation was protective against pulmonary inflammation when initiated after the inflammatory stimulus. In conclusion, nonmyeloid HO-1 is crucial for the anti-inflammatory effect of this enzyme on PMN migration to different compartments of the lung and on microvascular permeability.
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Germany (DE)How to cite
APA:
Konrad, F.M., Knausberg, U., Hoene, R., Ngamsri, K.-C., & Reutershan, J. (2016). Tissue heme oxygenase-1 exerts anti-inflammatory effects on LPS-induced pulmonary inflammation. Mucosal Immunology, 9(1), 98-111. https://dx.doi.org/10.1038/mi.2015.39
MLA:
Konrad, F. M., et al. "Tissue heme oxygenase-1 exerts anti-inflammatory effects on LPS-induced pulmonary inflammation." Mucosal Immunology 9.1 (2016): 98-111.
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