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Published online before print December 11, 2007

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0907618

Received for publication September 11, 2007.
Revised November 2, 2007.
Accepted for publication November 6, 2007.

Article

Targeted deletion of cannabinoid receptors CB₁ and CB₂ produced enhanced inflammatory responses to influenza A/PR/8/34 in the absence and presence of ⁹-tetrahydrocannabinol

John P. Buchweitz ^*, Peer W. F. Karmaus , Kurt J. Williams , Jack R. Harkema , and Norbert E. Kaminski ^*@

Departments of *Pharmacology and Toxicology and Pathobiology and Diagnostic Investigation and Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan, USA

^@ To whom correspondence should be addressed. E-mail: kamins11{at}msu.edu.

	Abstract

We have previously reported that -9-tetrahydrocannabinol (⁹-THC)-treated mice challenged with influenza virus A/PR/8/34 (PR8) developed increased viral hemagglutinin 1 (H1) mRNA levels and decreased macrophage 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 ⁹-THC on immune and epithelial cell responses to PR8. In the current study, 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, ⁹-THC-treated CB₁^-/-/CB₂^-/- mice infected with PR8 had increased CD4⁺ T cells and IFN- in bronchoalveolar lavage fluid with greater pulmonary inflammation when compared with ⁹-THC-treated wild-type mice infected with PR8. 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 ⁹-THC-treated CB₁^-/-/CB₂^-/- and wild-type mice indicated the involvement of CB₁/CB₂ receptor-dependent and -independent mechanisms.

Key Words: mice • lung • influenza • inflammation

This article has been cited by other articles:

				A. E. B. Springs, P. W. F. Karmaus, R. B. Crawford, B. L. F. Kaplan, and N. E. Kaminski Effects of targeted deletion of cannabinoid receptors CB1 and CB2 on immune competence and sensitivity to immune modulation by {Delta}9-tetrahydrocannabinol J. Leukoc. Biol., December 1, 2008; 84(6): 1574 - 1584. [Abstract] [Full Text] [PDF]