science pharmaceutical expo biotech jobs
Originally published online as doi:10.1189/jlb.0508282 on September 12, 2008

Published online before print September 12, 2008
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jlb.0508282v1
84/6/1574    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Springs, A. E. B.
Right arrow Articles by Kaminski, N. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Springs, A. E. B.
Right arrow Articles by Kaminski, N. E.
(Journal of Leukocyte Biology. 2008;84:1574-1584.)
© 2008 by Society for Leukocyte Biology

Effects of targeted deletion of cannabinoid receptors CB1 and CB2 on immune competence and sensitivity to immune modulation by {Delta}9-tetrahydrocannabinol

Alison E. B. Springs*, Peer W. F. Karmaus*,{dagger}, Robert B. Crawford{dagger}, Barbara L. F. Kaplan* and Norbert E. Kaminski*,{dagger},1

* Center for Integrative Toxicology, Cell and Molecular Biology Program, and
{dagger} Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan, USA

1 Correspondence: Center for Integrative Toxicology and Department of Pharmacology and Toxicology, Michigan State University, 315 National Food Safety and Toxicology Building, East Lansing, MI 48824-1317, USA. E-mail: kamins11{at}msu.edu

The role of cannabinoid receptors, CB1 and CB2, in immune competence and modulation by {Delta}9-tetrahydrocannabinol ({Delta}9-THC) was investigated in CB1–/–/CB2–/– mice. Immunofluorescence analysis of splenic leukocytes showed no significant differences in the percentage of T cell subsets, B cells, or macrophages between wild-type and CB1–/–/CB2–/– mice. Lymphoproliferative control responses to PHA, phorbol ester plus ionomycin, or LPS and sensitivity to suppression by {Delta}9-THC showed no profound differences between the two genotypes, although some differences were observed in control baseline responses. Likewise, similar control responses and sensitivity to {Delta}9-THC were observed in mixed lymphocyte responses (MLR) and in IL-2 and IFN-{gamma} production in both genotypes. Conversely, humoral immune responses showed a markedly different profile of activity. {Delta}9-THC suppressed the in vivo T cell-dependent, anti-sheep RBC (anti-sRBC) IgM antibody-forming cell (AFC) response in wild-type but not in CB1–/–/CB2–/– mice, and the in vitro anti-sRBC IgM response in CB1–/–/CB2–/– splenocytes was too low to rigorously assess CB1/CB2 involvement in modulation by {Delta}9-THC. Conversely, comparable in vitro IgM AFC control responses to LPS and CD40 ligand (CD40L) activation were observed in the two genotypes. Interestingly, LPS-induced IgM responses were refractory to suppression by {Delta}9-THC, regardless of genotype, and CD40L-induced IgM responses were only suppressed by {Delta}9-THC in wild-type but not in CB1–/–/CB2–/– B cells. Collectively, we demonstrate differential involvement of CB1 and/or CB2 in immune modulation by {Delta}9-THC and in some control responses. Moreover, CB1/CB2 involvement was observed in humoral responses requiring CD40-initiated signaling for suppression by {Delta}9-THC.

Key Words: immunopharmacology • CD40 ligand • humoral immunity • cell-mediated immunity