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Fibronectin enhances the migration rate of human neutrophils in vitro
E A Everitt1, A B Malik, B Hendey
1Department of Pharmacology, Rush Medical College, Rush-Presbyterian-St. Luke's-Medical Center, Chicago, Illinois 60612, USA.
Abstract:
Efficient polymorphonuclear neutrophil (PMN) migration depends on specific interactions between PMNs, endothelial cells, and extracellular matrix (ECM) proteins. We investigated the relationship between PMN migration and the ECM molecule fibronectin (FN). We used an in vitro migration assay system to show that human PMNs migrated across an FN-coated filter barrier toward a formyl-Met-Leu-Phe (fMLP) chemoattractant gradient in greater numbers than across (uncoated) bare fitters. In 1 h of fMLP stimulation, 69 +/- 6% of the PMNs had migrated across the FN-coated filters, whereas 46 +/- 5% of PMNs migrated across bare filters. This effect was specific to FN; coating the filters with the ECM protein vitronectin did not enhance migration. Monoclonal antibodies against FN or against the alpha5 or beta1 integrin subunits of the FN receptor inhibited the enhanced PMN migration response across FN-coated filters. These findings indicate that the extracellular matrix protein FN enhances PMN migration and that this response is mediated by the alpha5beta1 FN receptor.
Insights
Polymorphonuclear neutrophil (PMN) migration is enhanced by fibronectin (FN), an extracellular matrix protein. This migration relies on the alpha5beta1 integrin receptor, crucial for immune cell movement.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Polymorphonuclear neutrophil (PMN) migration is vital for effective immune responses.
- PMN migration involves complex interactions with endothelial cells and extracellular matrix (ECM) proteins.
Purpose of the Study:
- To investigate the role of fibronectin (FN) in enhancing PMN migration.
- To determine the specific receptor mediating FN-enhanced PMN migration.
Main Methods:
- Utilized an in vitro migration assay system with human PMNs.
- Compared PMN migration across fibronectin-coated filters versus uncoated filters.
- Investigated the effect of monoclonal antibodies against FN and alpha5beta1 integrins.
Main Results:
- Human PMNs exhibited significantly enhanced migration across fibronectin-coated filters compared to bare filters.
- Fibronectin-specific enhancement of migration was observed, unlike with vitronectin.
- Monoclonal antibodies targeting FN or alpha5beta1 integrins inhibited the enhanced migration.
Conclusions:
- The extracellular matrix protein fibronectin enhances polymorphonuclear neutrophil migration.
- This enhancement is specifically mediated by the alpha5beta1 integrin receptor.