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Updated: Jun 18, 2026

Imaging G Protein-coupled Receptor-mediated Chemotaxis and its Signaling Events in Neutrophil-like HL60 Cells
Published on: September 14, 2016
G protein-coupled receptor 43 is essential for neutrophil recruitment during intestinal inflammation
Christian Sina1, Olga Gavrilova, Matti Förster
1Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Kiel, Germany.
Abstract:
Molecular danger signals attract neutrophilic granulocytes (polymorphonuclear leukocytes (PMNs)) to sites of infection. The G protein-coupled receptor (GPR) 43 recognizes propionate and butyrate and is abundantly expressed on PMNs. The functional role of GPR43 activation for in vivo orchestration of immune response is unclear. We examined dextrane sodium sulfate (DSS)-induced acute and chronic intestinal inflammatory response in wild-type and Gpr43-deficient mice. The severity of colonic inflammation was assessed by clinical signs, histological scoring, and cytokine production. Chemotaxis of wild-type and Gpr43-deficient PMNs was assessed through transwell cell chemotactic assay. A reduced invasion of PMNs and increased mortality due to septic complications were observed in acute DSS colitis. In chronic DSS colitis, Gpr43(-/-) animals showed diminished PMN intestinal migration, but protection against inflammatory tissue destruction. No significant difference in PMN migration and cytokine secretion was detected in a sterile inflammatory model. Ex vivo experiments show that GPR43-induced migration is dependent on activation of the protein kinase p38alpha, and that this signal acts in cooperation with the chemotactic cytokine keratinocyte chemoattractant. Interestingly, shedding of L-selectin in response to propionate and butyrate was compromised in Gpr43(-/-) mice. These results indicate a critical role for GPR43-mediated recruitment of PMNs in containing intestinal bacterial translocation, yet also emphasize the bipotential role of PMNs in mediating tissue destruction in chronic intestinal inflammation.
Insights
G protein-coupled receptor 43 (GPR43) plays a dual role in intestinal inflammation. While essential for recruiting neutrophils to fight infection, it also contributes to tissue damage in chronic conditions.
Area of Science:
- Immunology
- Gastroenterology
- Molecular Biology
Background:
- Neutrophilic granulocytes (polymorphonuclear leukocytes, PMNs) are crucial for combating infection.
- G protein-coupled receptor 43 (GPR43), which binds propionate and butyrate, is highly expressed on PMNs.
- The in vivo function of GPR43 in immune responses remains largely undefined.
Purpose of the Study:
- To investigate the role of GPR43 in dextrane sodium sulfate (DSS)-induced acute and chronic intestinal inflammation.
- To elucidate the molecular mechanisms underlying GPR43-mediated PMN migration.
Main Methods:
- Utilized wild-type and Gpr43-deficient mice in DSS-induced colitis models.
- Assessed colonic inflammation severity through clinical signs, histology, and cytokine analysis.
- Evaluated PMN chemotaxis ex vivo using transwell assays and analyzed signaling pathways.
Main Results:
- Gpr43(-/-) mice exhibited increased mortality and reduced PMN invasion in acute DSS colitis.
- In chronic DSS colitis, Gpr43(-/-) mice showed decreased PMN migration but were protected from tissue damage.
- GPR43-mediated PMN migration involved p38alpha kinase and keratinocyte chemoattractant, and affected L-selectin shedding.
Conclusions:
- GPR43 is critical for recruiting PMNs to control bacterial translocation in the gut.
- PMNs, via GPR43, have a bipotential role, contributing to both host defense and tissue destruction in chronic inflammation.
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