PMID- 28497923 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 2092-7355 (Print) IS - 2092-7363 (Electronic) IS - 2092-7355 (Linking) VI - 9 IP - 4 DP - 2017 Jul TI - CCR3 Monoclonal Antibody Inhibits Eosinophilic Inflammation and Mucosal Injury in a Mouse Model of Eosinophilic Gastroenteritis. PG - 360-367 LID - 10.4168/aair.2017.9.4.360 [doi] AB - PURPOSE: Although the role of eosinophils in eosinophilic gastroenteritis (EGE) is not fully understood, they are believed to be a principal effector cell. Previous studies have demonstrated that eotaxin and its specific receptor, cysteine-cysteine chemokine receptor-3 (CCR3), play a central role in eosinophil trafficking into the gastrointestinal (GI) tract. Thus, we examined the targeting of CCR3 as a potential therapeutic intervention for EGE in a mouse model. METHODS: Eight- to 10-week-old BALB/c mice were intraperitoneally sensitized and intragastrically challenged with ovalbumin (OVA). Different groups of mice were administered either an anti-CCR3 antibody or a control IgG by intraperitoneal injection 1 hour before each OVA challenge. Eosinophilic inflammation in the intestinal mucosa, mucosal injury, and severity of diarrhea were compared between different groups at 1 hour after final OVA challenge. RESULTS: Anti-CCR3 antibody reduced the number of eosinophils in peripheral blood and intestinal mucosa, but not in bone marrow. This reduction was associated with restoration of reduced villous crypt ratio, increased intestinal epithelial cell proliferation, and weight loss induced by OVA challenge. However, Anti-CCR3 antibody had no effect on the level of OVA specific immunoglobulin E (IgE) and the expression of critical chemokines or cytokines in eosinophil trafficking into the GI tract, such as eotaxin-1, interleukin (IL)-5, and IL-13. CONCLUSIONS: Anti-CCR3 antibody significantly reduced the severity of eosinophilic inflammation, mucosal injury, and diarrhea in a mouse model of food allergen-induced GI eosinophilic inflammation. CCR3 may be a novel therapeutic target for treatment of EGE and other GI eosinophil-mediated diseases. CI - Copyright (c) 2017 The Korean Academy of Asthma, Allergy and Clinical Immunology . The Korean Academy of Pediatric Allergy and Respiratory Disease FAU - Song, Dae Jin AU - Song DJ AD - Department of Pediatrics, Korea University College of Medicine, Seoul, Korea. AD - Environmental Health Center for Childhood Asthma, Korea University Anam Hospital, Seoul, Korea. djsong506@korea.ac.kr. FAU - Shim, Mun Hee AU - Shim MH AD - Department of Pediatrics, Korea University College of Medicine, Seoul, Korea. FAU - Lee, Nahyun AU - Lee N AD - Department of Pediatrics, Korea University College of Medicine, Seoul, Korea. FAU - Yoo, Young AU - Yoo Y AD - Department of Pediatrics, Korea University College of Medicine, Seoul, Korea. AD - Environmental Health Center for Childhood Asthma, Korea University Anam Hospital, Seoul, Korea. FAU - Choung, Ji Tae AU - Choung JT AD - Department of Pediatrics, Korea University College of Medicine, Seoul, Korea. AD - Environmental Health Center for Childhood Asthma, Korea University Anam Hospital, Seoul, Korea. LA - eng PT - Journal Article PL - Korea (South) TA - Allergy Asthma Immunol Res JT - Allergy, asthma & immunology research JID - 101518382 PMC - PMC5446951 OTO - NOTNLM OT - CCR3 OT - eosinophilic gastroenteritis OT - eosinophils COIS- There are no financial or other issues that might lead to conflict of interest. EDAT- 2017/05/13 06:00 MHDA- 2017/05/13 06:01 PMCR- 2017/07/01 CRDT- 2017/05/13 06:00 PHST- 2016/09/11 00:00 [received] PHST- 2017/01/31 00:00 [revised] PHST- 2017/01/31 00:00 [accepted] PHST- 2017/05/13 06:00 [entrez] PHST- 2017/05/13 06:00 [pubmed] PHST- 2017/05/13 06:01 [medline] PHST- 2017/07/01 00:00 [pmc-release] AID - 9.360 [pii] AID - 10.4168/aair.2017.9.4.360 [doi] PST - ppublish SO - Allergy Asthma Immunol Res. 2017 Jul;9(4):360-367. doi: 10.4168/aair.2017.9.4.360.