Heme oxygenase-1 inhibits basophil maturation and activation but promotes its apoptosis in T helper type 2-mediated allergic airway inflammation.

Abstract

The anti-inflammatory role of heme oxygenase-1 (HO-1) has been studied extensively in many disease models including asthma. Many cell types are anti-inflammatory targets of HO-1, such as dendritic cells and regulatory T cells. In contrast to previous reports that HO-1 had limited effects on basophils, which participate in T helper type 2 immune responses and antigen-induced allergic airway inflammation, we demonstrated in this study, for the first time, that the up-regulation of HO-1 significantly suppressed the maturation of mouse basophils, decreased the expression of CD40, CD80, MHC-II and activation marker CD200R on basophils, blocked DQ-ovalbumin uptake and promoted basophil apoptosis both in vitro and in vivo, leading to the inhibition of T helper type 2 polarization. These effects of HO-1 were mimicked by exogenous carbon monoxide, which is one of the catalytic products of HO-1. Furthermore, adoptive transfer of HO-1-modified basophils reduced ovalbumin-induced allergic airway inflammation. The above effects of HO-1 can be reversed by the HO-1 inhibitor Sn-protoporphyrin IX. Moreover, conditional depletion of basophils accompanying hemin treatment further attenuated airway inflammation compared with the hemin group, indicating that the protective role of HO-1 may involve multiple immune cells. Collectively, our findings demonstrated that HO-1 exerted its anti-inflammatory function through suppression of basophil maturation and activation, but promotion of basophil apoptosis, providing a possible novel therapeutic target in allergic asthma.

• Authors: Wenwei Zhong, Caixia Di, Jiajia Lv, Yanjie Zhang, Xiaoliang Lin, Yufan Yuan, Jie Lv, Zhenwei Xia
• Journal: Immunology (Immunology) Vol. 147 Issue 3 Pg. 321-37 (Mar 2016) ISSN: 1365-2567 [Electronic] England
• PMID: 26879758 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons Ltd.

Chemical References

• Membrane Proteins
• Heme Oxygenase-1
• Hmox1 protein, mouse

Topics

• Adoptive Transfer
• Animals
• Apoptosis (immunology)
• Asthma (immunology)
• Basophils (immunology)
• Enzyme-Linked Immunosorbent Assay
• Flow Cytometry
• Heme Oxygenase-1 (immunology)
• Hypersensitivity (immunology)
• Immunohistochemistry
• Inflammation (immunology)
• Membrane Proteins (immunology)
• Mice
• Mice, Inbred BALB C
• Real-Time Polymerase Chain Reaction
• Th2 Cells (immunology)