Cellular softening mediates leukocyte demargination and trafficking, thereby increasing clinical blood counts
Abstract
Clinical hematologists have long known that antiinflammatory glucocorticoids such as dexamethasone and blood pressure-supporting catecholamines such as epinephrine cause leukocytes to demarginate from the vascular wall and microvasculature into the main circulation, significantly elevating the effective white blood cell count. Canonically, this has been attributed to down-regulation of adhesion molecules such as selectins, but we show that a purely mechanical phenomenon caused by leukocyte softening plays a major role as well. Our work provides an answer to an old hematological problem and reveals a mechanism in which the immune system simply alters leukocyte stiffness to regulate leukocyte trafficking. This has clinically relevant implications for the inflammatory process overall as well as for hematopoietic stem cell mobilization and homing.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- February 2016
- DOI:
- 10.1073/pnas.1508920113
- Bibcode:
- 2016PNAS..113.1987F