408 G.A. Cabral and A. Staab
in CB 1 mRNA expression in mouse splenocytes. It was suggested that signaling
pathways activated by T cell mitogens led to decreased CB 1 gene activation while
pathways activated by B cell mitogens and IL-2 led to increased levels of CB 1 .Leeet
al. (2001a,b) examined the expression pattern of CB 2 mRNA in mouse peritoneal
macrophages. CB 2 was expressed in thioglycolate-elicited macrophages, but not
in resident macrophages. LPS stimulation down-regulated CB 2 mRNA expression
in splenocyte cultures, while stimulation through CD40 using anti-CD40 antibody
up-regulated the response. In addition, co-stimulation with IL-4 attenuated the
anti-CD40 response. Collectively, the results suggested that the signaling path-
ways activated by LPS and anti-CD40 exerted differential effects on CB 2 mRNA
expression. Carlisle et al. (2002) indicated that the CB 2 receptor was differentially
expressed by rodent peritoneal macrophages and macrophage-like cells in rela-
tion to their cell activation state. The CB 2 receptor was undetectable in resident
macrophages, present at high levels in thioglycolate-elicited inflammatory and
IFN-γ-primed macrophages, and detected at significantly diminished levels in LPS
fully activated macrophages. A comparable pattern of differential expression of the
CB 2 receptor was noted for murine macrophage-like cells and neonatal rat brain
cortex microglia.
5.2
Distribution in Cell Lines
Messenger RNA for CB 1 has been found in immune cell lines, including human
THP-1 monocytic cells, human Raji B cells, murine NKB61A2 NK-like cells, and
murine CTLL2 IL-2-dependent T cells (Daaka et al. 1995). Sinha et al. (1998)
employed RT-PCR to detect message and affinity-purified polyclonal antiserum to
demonstrate that MHC class II+, macrophage-like, glial cells contained message
and cognate protein for CB 1. A glioma cell line and a B lymphoblastoid cell line
also were positive for this protein, which was estimated at 58 kDa. Daaka et al.
(1996) indicated that the Jurkat, human T cell line was weakly positive for the
CB 1 receptor but mitogen activation increased message levels. Valk et al. (1997)
reported the presence of CB 2 mRNA in 45 of 51 cell lines of distinct hematopoietic
lineages, including myeloid, macrophage, mast, B lymphoid, T lymphoid, and
erythroidcells.ArankorderforlevelsofCB 2 transcripts similar to that for primary
human cell types has been recorded for human cell lines belonging to the myeloid,
monocytic, and lymphoid lineages (Bouaboula et al. 1993).
6
Mode of Action in the Immune System
6.1
Exogenous Cannabinoids
Smith et al. (1978) were among the first to note structure–activity relationships of
natural and synthetic cannabinoids in suppression of humoral and cell-mediated