Surface receptor-mediated adhesion is a fundamental step in the recruitment of leukocytes and platelets, as well as platelet–leukocyte interactions. The surface receptor CD147 is crucially involved in host defense against self-derived and invading targets, as well as in thrombosis. In the current study, we describe the previously unknown interaction of CD147 with integrin αMβ2 (Mac-1) in this context. Using binding assays, we were able to show a stable interaction of CD147 with Mac-1 in vitro. Leukocytes from Mac-1^−/− and CD147^+/− mice showed a markedly reduced static adhesion to CD147- and Mac-1-coated surfaces, respectively, compared to wild-type mice. Similarly, we observed reduced rolling and adhesion of monocytes under flow conditions when cells were pre-treated with antibodies against Mac-1 or CD147. Additionally, as assessed by antibody inhibition experiments, CD147 mediated the dynamic adhesion of platelets to Mac-1-coated surfaces. The interaction of CD147 with Mac-1 is a previously undescribed mechanism facilitating the adhesion of leukocytes and platelets.

The endocannabinoid 2-arachidonoylglycerol (2-AG) is an inflammatory mediator and ligand for the cannabinoid receptors CB1 and CB2. We investigated the atherogenic mechanisms set in motion by 2-AG. Therefore, we created two atherosclerotic mouse models with distinct cell-specific knockouts of the CB2 receptor on either myeloid or endothelial cells. These mice were treated with JZL184, resulting in elevated plasma levels of 2-AG. After a high-fat high-cholesterol diet, atherosclerotic plaques were analyzed. The atherogenic effect of 2-AG was abrogated in mice lacking myeloid expression of the CB2 receptor but not in mice lacking endothelial expression of the CB2 receptor. In vitro, treatment of human monocytes with 2-AG led to the increased production of reactive oxygen species (ROS) and IL-1β. In conclusion, 2-AG shows an atherogenic effect in vivo, dependent on the presence of the CB2 receptor on myeloid cells. In addition, our in vitro data revealed 2-AG to promote inflammatory signalling in monocytes. Graphical abstract 2-Arachidonoylglycerol shows an atherogenic effect that is abrogated in mice lacking myeloid expression of the CB2 receptor.

Introduction: GPR30 is an intracellular transmembrane G protein-coupled receptor that mediates non-genomic estrogen signaling. The GPR30 agonist G-1 modulates glucose homeostasis and vascular function. However, its impact on vascular inflammation and atherogenesis has not yet been investigated...

2-arachidonoylglycerol (2-AG) is an endogenous modulator of inflammatory processes. Recent studies demonstrate its key role in inflammatory cardiovascular diseases, such as atherosclerosis and left ventricular remodelling. However, whether 2-AG acts as a pro- or anti-inflammatory agent in cardiovascular inflammation is a matter of controversial debate. CD14 ⁺ primary human monocytes were treated with 2-AG. Differentially expressed genes were determined by mRNA sequencing and used for bioinformatics analysis of changes in myeloid cell functions and cell signalling pathways. Additionally, we quantified cytokines and mediators involved in cardiac remodelling by multiplexing assays. Human monocytes responded to the treatment with 2-AG by inducing a pro-inflammatory cellular program. The top upregulated hallmark pathways were TNFα signalling via the NF-κB pathway, the inflammatory response and IL-6 signalling, illustrating the pro-inflammatory mode of action of 2-AG. These data were validated at the protein level in the supernatants of stimulated cells using multiplexing assays. Based on these in-vitro results, we examined blood samples from patients during acute and chronic coronary syndromes. By sampling blood from both the periphery and the culprit coronary artery, we observed a trend towards higher local concentrations of the cardiac remodelling factors Galectin-3, Osteopontin, and IP-10 in the coronary arteries of patients presenting with acute coronary syndrome compared with other groups. The levels of these remodelling factors correlate positively with 2-AG levels. Taken together, our data suggest that 2-AG acts as a pro-inflammatory agent in myocardial infarction and LV remodelling.