title: Endogenous cannabinoids and neutrophil chemotaxis.
abstract: Neutrophils are the earliest inflammatory cell to infiltrate tissue, playing an important role in early phagocytosis. Under pathological conditions, pro-inflammatory actions of neutrophils contribute to the development of various inflammatory diseases. G(i) protein-coupled cell-surface receptors are an essential component of pro-migratory responses in leukocytes; however, few investigations regarding inhibitors of cell migration have been reported. Kurihara et al. (2006) and McHugh et al. (2008) have revealed that certain endogenous cannabinoids and lipids are potent inhibitors of induced human neutrophil migration. McHugh et al. implicate a novel SR141716A-sensitive pharmacological target distinct from cannabinoid CB(1) and CB(2) receptors, which is antagonized by N-arachidonoyl-l-serine; and that the CB(2) receptor exerts negative co-operativity upon this receptor. Kurihara et al. demonstrate that fMLP-induced RhoA activity is decreased following endocannabinoid pretreatment, disrupting the front/rear polarization necessary for neutrophils to engage in chemotaxis. The therapeutic potential of exploiting endocannabinoids as neutrophilic chemorepellants is plain to see.
authors: Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, USA.
authors: Douglas
authors: D
authors: McHugh
authors: Ruth A
authors: RA
authors: Ross
mesh_terms: D000199:Actins / Q000737:chemistry; D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D003599:Cytoskeleton / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D009504:Neutrophils / Q000502:physiology*; D020239:Receptor Cross-Talk / Q000502:physiology; D043882:Receptors, Cannabinoid / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000199:Actins; D063385:Cannabinoid Receptor Modulators; D043882:Receptors, Cannabinoid