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G. Zuchtriegel et al.
suggesting that these selectin- and integrin-mediated molecular events (already occurring at the initial stages of the leukocyte recruitment process) are not sufficient for the stabilization of intravascular adhesion of neu- trophils, but might prepare this critical step in the extravasation cascade of these immune cells.
In conclusion, our experimental data indicate that the heteromerization of VN with PAI-1 on the microvascular endothelium of inflamed tissue represents a critical event for the extravasation process of neutrophils that substan- tially controls the transition of dynamic to static endothe- lial interactions of these immune cells. To this end, VN- PAI-1 heteromers promote the surface clustering of b2 integrins on adhering neutrophils, thus enabling effective neutrophil responses (Figure 7). Targeting this process might be beneficial for the prevention and treatment of inflammatory diseases.
Disclosures
No conflicst of interest to disclose.
Contributions
GZ, BU, RP, MP, JD, LM performed experiments and data analysis; MC, SK, MS, FK, CAR wrote the manuscript and CAR supervised the study.
Acknowledgements
The authors thank Susanne Bierschenk for excellent technical assistance. Data presented in this study are part of the doctoral thesis of MR.
Funding
This study was supported by Deutsche Forschungsgemeinschaft (DFG), Sonderforschungsbereich (SFB) 914, projects Z03 (to MS), B01 (to MS), and B03 (to CAR).
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