Ethanol promotes protease activated receptor 1: Chemokine (C-X-C motif) receptor 4 heteromerization and enhances thrombin-induced impairment of human lung endothelial cell barrier function.

Ethanol enhances the propensity of PAR1 and CXCR4 to form heteromers. Ethanol increases PAR1:CXCR4 heteromer expression in human lung microvascular endothelial cells (HULEC-5a). Ethanol enhances the efficacy of PAR1 to activate Gα upon thrombin stimulation in cells co-expressing CXCR4.

Chemokine receptor hetero-oligomers regulate monocyte chemotaxis.

It is known that stress influences immune cell function. The underlying molecular mechanisms are unclear. We recently reported that many chemokine receptors (CRs) heteromerize with α-adrenoceptors (α-ARs) through which CRs are regulated.

Effects of chemokine (C-C motif) receptor 2 and 3 antagonists in rat models of hemorrhagic shock.

Systemic concentrations of chemokine CCL2, an agonist at chemokine receptors CCR2/3/5, have been associated with hemodynamic instability after traumatic-hemorrhagic shock. We reported previously that the CCR2 antagonist INCB3284 prevents cardiovascular collapse and reduces fluid requirements after 30min of hemorrhagic shock (HS), whereas the CCR5 antagonist Maraviroc was ineffective. The effects of CCR3 blockade after HS are unknown and information on the therapeutic potential of INCB3284 after longer periods of HS and in HS models in the absence of fluid resuscitation (FR) is lacking.

α-adrenoceptor ligands inhibit chemokine receptor heteromerization partners of α-adrenoceptors via interference with heteromer formation.

We reported previously that α-adrenoceptor (α-AR) ligands inhibit chemokine receptor (CR) heteromerization partners of α-AR. The underlying mechanisms are unknown and in vivo evidence for such effects is missing. Utilizing CCR2 and α-AR as prototypical partners, we observed in recombinant systems and THP-1 cells that α-AR enhanced whereas its absence inhibited Gαi signaling of CCR2.

Heteromerization between α -adrenoceptor and chemokine (C-C motif) receptor 2 biases α -adrenoceptor signaling: Implications for vascular function.

Previously, we reported that chemokine (C-C motif) receptor 2 (CCR2) heteromerizes with α -adrenoceptor (α -AR) in leukocytes, through which α -AR controls CCR2. Whether such heteromers are expressed in human vascular smooth muscle cells (hVSMCs) is unknown. Bioluminescence resonance energy transfer confirmed formation of recombinant CCR2:α -AR heteromers.