Targeted deletion of cannabinoid receptors CB1 and CB2 produced enhanced inflammatory responses to influenza A/PR/8/34 in the absence and presence of Δ9-tetrahydrocannabinol

被引：44
作者：
Buchweitz, John P. [1 ,3 ]
Karmaus, Peer W. F. [3 ]
Williams, Kurt J. [2 ]
Harkema, Jack R. [2 ,3 ]
Kaminski, Norbert E. [1 ,3 ]
机构：
[1] Michigan State Univ, Dept Pharmacol & Toxicol, E Lansing, MI 48824 USA
[2] Michigan State Univ, Dept Pathobiol & Diagnost Invest, E Lansing, MI 48824 USA
[3] Michigan State Univ, Ctr Integrat Toxicol, E Lansing, MI 48824 USA
来源：
JOURNAL OF LEUKOCYTE BIOLOGY | 2008年 / 83卷 / 03期
关键词：
mice; lung; influenza; inflammation;
D O I：
10.1189/jlb.0907618
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
We have previously reported that Delta-9tetrahydrocannabinol (Delta(9)-THC)-treated mice challenged with influenza virus A/PR/8/34 (PR8) developed increased viral hemagglutinin 1 (H1) mRNA levels and decreased monocyte and lymphocyte recruitment to the pulmonary airways when compared with mice challenged with PR8 alone. The objective of the present study was to examine the role of cannabinoid (CB1/CB2) receptors in mediating the effects of Delta(9)-THC on immune and epithelial cell responses to PR8. In the current study, Delta(9)-THC-treated CB1/CB2 receptor null (CB1-/-/CB2-/-) and wild-type mice infected with PR8 had marked increases in viral H1 mRNA when compared with CB1-/-/CB2-/- and wild-type mice challenged with PR8 alone. However, the magnitude of the H1 mRNA levels was greatly reduced in CB1-/-/CB2-/- mice as compared with wild-type mice. In addition, Delta(9)-THC-treated CB1-/-/CB2-/- mice infected with PR8 had increased CD4(+) T cells and IFN-gamma in bronchoalveolar lavage fluid with greater pulmonary inflammation when compared with Delta(9)-THC-treated wild-type mice infected with PR8. Delta(9)-THC treatment of CB1-/-/CB2-/- mice in the presence or absence of PR8 challenge also developed greater amounts of mucous cell metaplasia in the affected bronchiolar epithelium. Collectively, the immune and airway epithelial cell responses to PR8 challenge in Delta(9)-THC-treated CB1-/-/CB2-/- and wild-type mice indicated the involvement of CB1/CB2 receptor-dependent and-independent mechanisms.
引用
收藏
页码：785 / 796
页数：12
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