In vivo and in vitro treatment with the synthetic cannabinoid CP55,940 decreases the in vitro migration of macrophages in the rat: involvement of both CB1 and CB2 receptors

Cannabinoids have been shown to affect immune responses, acting on differen t populations of immune cells. In the present paper we analyze the ability of in vivo and in vitro treatment with the potent synthetic cannabinoid CP5 5,940 to interfere with an important function of rat peritoneal macrophages , i.e. spontaneous migration and formyl-metionyl-leucine-phenylalanine (fML P)-induced chemotaxis, that were assessed by the use of a Boyden-modified m icrochemotaxis chamber. When added in vitro, CP55,940 induced a significant and dose-dependent inhibition of both spontaneous migration and fMLP-induc ed chemotaxis. Both the Cannabinoid Receptor 1 (CB1) and the Cannabinoid Re ceptor 2 (CB2) antagonists were able to block the CP55,940-induced inhibiti on of spontaneous migration, although the CB2 antagonist was more potent an d only the CB2 antagonist was able to reverse the effect of CP55,940 on fML P-induced chemotaxis. Similarly, in the in vivo experiments, 1 h after the acute subcutaneous administration of 0.4 mg/kg of CP55,940, both spontaneou s motility and chemotaxis were reduced. The pretreatment with the CB2 antag onist, but not with the CB1 antagonist, was able to prevent this effect. Ou r data confirm that cannabinoids can affect some macrophage functions, main ly throughout CB2 receptors, and suggest that the development of specific C B2 ligands may lead to an interesting new class of anti-inflammatory drugs. (C) 2000 Elsevier Science BN. All rights reserved.