Migrating Myeloid Cells Sense Temporal Dynamics of Chemoattractant Concentrations
Autor: | Justine S. Yoon, Yun M. Zhao, Caren E. Petrie Aronin, Thorsten Prüstel, Ronald N. Germain, Nicole Y. Morgan, Martin Meier-Schellersheim |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Chemokine G-Protein-Coupled Receptor Kinase 3 Myeloid Microfluidics Immunology Motility Mice 03 medical and health sciences 0302 clinical medicine Cell Movement medicine Animals Immunology and Allergy Myeloid Cells Receptor Chemotactic Factors biology CCL19 Cell migration Chemotaxis Dendritic Cells G-Protein-Coupled Receptor Kinases Chemokine CXCL12 Cell biology Mice Inbred C57BL Haematopoiesis 030104 developmental biology Infectious Diseases medicine.anatomical_structure biology.protein Chemokine CCL19 030215 immunology |
Zdroj: | Immunity. 47:862-874.e3 |
ISSN: | 1074-7613 |
DOI: | 10.1016/j.immuni.2017.10.020 |
Popis: | Chemoattractant-mediated recruitment of hematopoietic cells to sites of pathogen growth or tissue damage is critical to host defense and organ homeostasis. Chemotaxis is typically considered to rely on spatial sensing, with cells following concentration gradients as long as these are present. Utilizing a microfluidic approach, we found that stable gradients of intermediate chemokines (CCL19 and CXCL12) failed to promote persistent directional migration of dendritic cells or neutrophils. Instead, rising chemokine concentrations were needed, implying that temporal sensing mechanisms controlled prolonged responses to these ligands. This behavior was found to depend on G-coupled receptor kinase-mediated negative regulation of receptor signaling and contrasted with responses to an end agonist chemoattractant (C5a), for which a stable gradient led to persistent migration. These findings identify temporal sensing as a key requirement for long-range myeloid cell migration to intermediate chemokines and provide insights into the mechanisms controlling immune cell motility in complex tissue environments. |
Databáze: | OpenAIRE |
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