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Targeted deletion of cannabinoid receptors CB 1 and CB 2 produced enhanced inflammatory responses to influenza A/PR/8/34 in the absence and presence of Δ 9 ‐tetrahydrocannabinol
Author(s) -
Buchweitz John P.,
Karmaus Peer W. F.,
Williams Kurt J.,
Harkema Jack R.,
Kaminski Norbert E.
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0907618
Subject(s) - biology , receptor , immune system , bronchoalveolar lavage , immunology , hemagglutinin (influenza) , delta 9 tetrahydrocannabinol , cannabinoid , monocyte , microbiology and biotechnology , medicine , lung , virus , biochemistry
We have previously reported that Δ‐9‐tetrahydrocannabinol (Δ 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 (CB 1 /CB 2 ) receptors in mediating the effects of Δ 9 ‐THC on immune and epithelial cell responses to PR8. In the current study, Δ 9 ‐THC‐treated CB 1 /CB 2 receptor null (CB 1 −/− /CB 2 −/− ) and wild‐type mice infected with PR8 had marked increases in viral H1 mRNA when compared with CB 1 −/− /CB 2 −/− and wild‐type mice challenged with PR8 alone. However, the magnitude of the H1 mRNA levels was greatly reduced in CB 1 −/− /CB 2 −/− mice as compared with wild‐type mice. In addition, Δ 9 ‐THC‐treated CB 1 −/− /CB 2 −/− mice infected with PR8 had increased CD4 + T cells and IFN‐γ in bronchoalveolar lavage fluid with greater pulmonary inflammation when compared with Δ 9 ‐THC‐treated wild‐type mice infected with PR8. Δ 9 ‐THC treatment of CB 1 −/− /CB 2 −/− 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 Δ 9 ‐THC‐treated CB 1 −/− /CB 2 −/− and wild‐type mice indicated the involvement of CB 1 /CB 2 receptor‐dependent and ‐independent mechanisms.