CCR3 antagonist impairs estradiol-induced eosinophil migration to the uterus in ovariectomized mice

Abstract

Eosinophils are abundant in the reproductive tract, contributing to the remodeling and successful implantation of the embryo. However, the mechanisms by which eosinophils migrate into the uterus and their relationship to edema are still not entirely clear, since there are a variety of chemotactic factors that can cause migration of these cells. Therefore, to evaluate the role of CCR3 in eosinophil migration, ovariectomized C57BL/6 mice were treated with CCR3 antagonist SB 328437 and 17β-estradiol. The hypothesis that the CCR3 receptor plays an important role in eosinophil migration to the mouse uterus was confirmed, because we observed reduction in eosinophil peroxidase activity in these antagonist-treated uteruses. The antagonist also influenced uterine hypertrophy, inhibiting edema formation. Finally, histological analysis of the orcein-stained uteruses showed that the antagonist reduced eosinophil migration together with edema. These data showed that the CCR3 receptor is an important target for studies that seek to clarify the functions of these cells in uterine physiology.

In Silico Identification of Cholesterol Binding Motifs in the Chemokine Receptor CCR3

“…The highest average scoring truncated model based on MolProbity scores [ 56 ], PROCHECK Ramachandran analysis [ 57 ], and ProSa [ 59 ] Z-score comparison to experimentally determined X-Ray crystallography and NMR structures was chosen ( Figure S2 , Table S1 ). We validated this structure via docking of a known CCR3 agonist (CH0076989) and several antagonists (UCB35625, YM344031, SB328437) [ 60 , 61 , 62 ] using Autodock Vina [ 36 ]. As a final step, these results were then compared to negative controls that shared some common features with the known ligands ( Figure 1 b).…”

“…Ramachandran analysis was performed using MolProbity and PROCHECK [ 57 ], and Z-score comparison to experimentally determined structures was performed with ProSa [ 58 , 59 ] for both the selected and truncated model and the CCR5 template ( Table S1 , Figure S2 ). Small molecules UCB35625 (ZINC13862637) [ 60 ], YM344031 (ZINC209227900) [ 61 ], SB328437 (ZINC59618358) [ 62 ], CH0076989 (ZINC1000177021) [ 60 ], Melatonin (ZINC57060), Serotonin (ZINC57058), L-Dopa (ZINC895199), Phenylethylamine (ZINC6579654), Dopamine (ZINC33882), Glutamine (ZINC1532526), Histamine (ZINC388081), and Glycine (ZINC465855) were downloaded from the ZINC database (accessed 1 October 2020) [ 63 ] ( Figure S3 ) and, along with the CCR3 model, prepared for docking analysis with AutoDock tools from the MGL Tools package (version 1.5.6, Molecular Graphics Lab, Scripps Research Institute, La Jolla, CA, USA) [ 64 ]. For CCR3, water was deleted, polar-only hydrogens were added, and Kollman charges were added.…”

Acupuncture for Primary Dysmenorrhea: A Potential Mechanism from an Anti-Inflammatory Perspective

“…Besides, EOS can regulate local immune and inflammatory responses and play a key role in PD induction and development. e elevated levels of eotaxin can also cause EOS migration to the uterus, promoting inflammatory edema and congestion in this organ [75]. Eosinophil cationic protein (ECP), major basic protein Evidence-Based Complementary and Alternative Medicine (MBP), neurotoxin, and eosinophil peroxidase released by activated EOS can also cause the release of reactive oxygen species (ROS) and cytotoxic molecules, promoting inflammation and inducing endothelial damage to activated platelets, which lead to vasoconstriction and blood clotting and ultimately reduced blood flow and aggravated PD.…”

Acupuncture Alleviates Menstrual Pain in Rat Model via Suppressing Eotaxin/CCR3 Axis to Weak EOS-MC Activation

“…The involvement of eosinophils in the female reproductive tract has been reported since the 1960s [ 44 ]. Also, in recent years, the role of EOS in the reproductive system has attracted a lot of attention [ 7 , 8 , 15 , 36 ]. Studies found that EOS became evident prior to and during menstruation [ 7 – 9 ].…”

“…The specific CCR3 agonist CCL11 (420-ME-100/CF, R&D Systems, MN, USA), which was reconstituted at 100 μ g/mL in sterile PBS (Vehicle2), was injected intraperitoneally at a dose of 10 μ g/per animal 30 min before the acupuncture. The dosage and route of drug administration were based on the previous study with certain minor modifications according to the experimental condition [ 36 ].…”