GPR35 promotes neutrophil recruitment in response to serotonin metabolite 5-HIAA
| Autor: | Marco De Giovanni, Hanson Tam, Colin Valet, Ying Xu, Mark R. Looney, Jason G. Cyster |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Blood Platelets
Serotonin Neutrophils 1.1 Normal biological development and functioning mast cells Ligands migration Cardiovascular Medical and Health Sciences Article GPCRs General Biochemistry Genetics and Molecular Biology Receptors G-Protein-Coupled Mice G-Protein-Coupled Underpinning research Receptors Humans Animals SSRI 2.1 Biological and endogenous factors Mast Cells Aetiology Inflammation Inflammatory and immune system 5-HIAA neutrophil serotonin metabolite Hydroxyindoleacetic Acid Biological Sciences Neutrophil Infiltration platelets GPR35 Developmental Biology |
| Zdroj: | Cell, vol 185, iss 5 Cell Cell, vol 185, iss 6 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2022.01.010 |
| Popis: | Rapid neutrophil recruitment to sites of inflammation is crucial for innate immune responses. Here, we reveal that the G-protein-coupled receptor GPR35 is upregulated in activated neutrophils, and it promotes their migration. GPR35-deficient neutrophils are less recruited from blood vessels into inflamed tissue, and the mice are less efficient in clearing peritoneal bacteria. Using a bioassay, we find that serum and activated platelet supernatant stimulate GPR35, and we identify the platelet-derived serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) as a GPR35 ligand. GPR35 function in neutrophil recruitment is strongly dependent on platelets, with the receptor promoting transmigration across platelet-coated endothelium. Mast cells also attract GPR35+ cells via 5-HIAA. Mice deficient in 5-HIAA show a loss of GPR35-mediated neutrophil recruitment to inflamed tissue. These findings identify 5-HIAA as a GPR35 ligand and neutrophil chemoattractant and establish a role for platelet- and mast cell-produced 5-HIAA in cell recruitment to the sites of inflammation and bacterial clearance. |
| Databáze: | OpenAIRE |
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