A novel mechanism of erythrocyte capture from circulation in humans.
OBJECTIVE
The capture of blood cells from the circulation is mediated by highly specialized adhesion molecules. These molecules contribute to the specificity of recruitment for various subsets. Here, we used a simple substrate of hyaluronic acid to investigate the specificity of CD44-mediated recruitment from human whole blood under shear conditions.


METHODS
Human whole blood was perfused through a parallel-plate flow chamber, which mimics intravascular conditions. Microscopy was used to directly observe blood-cell interactions with adhesion molecule substrates.


RESULTS
Erythrocytes, but not leukocytes, efficiently tethered to and rolled on the hyaluronic acid substrate. These interactions were demonstrated to be mediated by CD44 and regulated by the sialic acid content of the cells. Inflammatory stimuli did not result in enhanced erythrocyte rolling. Rather, interactions were restricted to aged erythrocytes approaching senescence. This mechanism of erythrocyte capture from the blood flow was found to be restricted to primates and not conserved across mammalian species.


CONCLUSIONS
This is the first report of erythrocyte tethering and rolling under shear conditions, a behavior, until now, thought to be exclusive to leukocytes. It may represent an important mechanism to identify, capture, and clear old erythrocytes during normal homeostasis or clot formation.
Institute of Infection, Immunity, and Inflammation, University of Calgary, Faculty of Medicine, Calgary, Alberta, Canada.
Steven M
SM
Kerfoot
Krista
K
McRae
Florence
F
Lam
Erin F
EF
McAvoy
Stephen
S
Clark
Michael
M
Brain
Patricia F
PF
Lalor
David H
DH
Adams
Paul
P
Kubes
D000818:Animals; D016922:Cellular Senescence; D004912:Erythrocytes / Q000378:metabolism* / Q000473:pathology; D006706:Homeostasis; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism*; D010477:Perfusion; D011323:Primates; D033081:Shear Strength; D013045:Species Specificity; D013927:Thrombosis / Q000378:metabolism* / Q000473:pathology
C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid