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Marijuana Suppresses Immune Response

The peripheral cannabinoid receptor (CB2) is a G protein-coupled receptor that is mainly expressed in immune cells. Because these cells are so diverse, it is assumed that CB2 is involved in a wide range of physiologic phenomena related to immunity. Among the possible roles for CB2 is the induction of leukocyte migration to sites of infection and inflammation. The investigation of this role is the subject of this Paper of the Week.

Using an in vitro model of neutrophil migration on blood vessels, Rina Kurihara and colleagues show that CB2 ligands induce increased motility in the cells. However, instead of developing the front/rear polarity typically exhibited by migrating leukocytes, the cells rapidly extended and retracted one or more pseudopods in different directions. Activity of the Rho-GTPase RhoA also decreased in response to CB2 stimulation, whereas Rac and Cdc42 activity increased. Human neutrophils did not experience increased motility or morphologic alterations in response to the ligands, but they did exhibit disrupted polarization and suppressed RhoA activity in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). These results suggest that CB2 might play a role in regulating excessive inflammatory response by controlling RhoA activation and thereby suppressing neutrophil migration.

JWH015-stimulated cells rapidly extend pseudopods.

FOOTNOTES

See referenced article, J. Biol. Chem. 2006, 281, 12908-12918

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