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The functional paradox of CD43 in leukocyte recruitment: a study using CD43-deficient mice
R C Woodman1, B Johnston, M J Hickey
1Immunology Research Group, University of Calgary, Calgary, Alberta, Canada T2N 4N1. woodman@acs.ucalgary.ca
Insights
Leukocyte CD43 (leukosialin) deficiency enhances leukocyte rolling and adhesion but impairs tissue infiltration. CD43 plays a dual role in leukocyte-endothelial interactions, acting as a barrier and facilitating emigration.
Area of Science:
- Immunology
- Cell Biology
- Microcirculation Research
Background:
- CD43 (leukosialin) is implicated in leukocyte cell-cell interactions, but its exact function is unclear.
- Understanding CD43's role is crucial for comprehending immune cell trafficking and inflammatory responses.
Purpose of the Study:
- To investigate the in vivo role of CD43 in leukocyte-endothelial cell interactions.
- To elucidate the specific functions of CD43 in leukocyte adhesion, rolling, and transmigration.
Main Methods:
- Utilized CD43-deficient mice (CD43(-/-)) and intravital microscopy to observe leukocyte behavior in the cremasteric microcirculation.
- Employed in vitro flow chambers with immobilized E-selectin to analyze leukocyte-substrate interactions.
- Assessed leukocyte infiltration into the peritoneum and emigration from vasculature in response to stimuli.
Main Results:
- CD43(-/-) mice exhibited significantly enhanced leukocyte rolling and adhesion compared to wild-type mice.
- Enhanced rolling of CD43(-/-) leukocytes on E-selectin suggested passive mechanisms like steric hindrance.
- Despite increased adhesion, CD43(-/-) leukocytes showed impaired infiltration into tissues and emigration from the vasculature.
Conclusions:
- Leukocyte CD43 possesses a dual function in leukocyte-endothelial interactions.
- CD43 acts as a passive functional barrier, influencing cell adhesion and rolling.
- CD43 is essential for facilitating leukocyte emigration into tissues, a previously unrecognized role.
Abstract:
Although there is considerable evidence implicating a role for CD43 (leukosialin) in leukocyte cell-cell interactions, its precise function remains uncertain. Using CD43-deficient mice (CD43(-/-)) and intravital microscopy to directly visualize leukocyte interactions in vivo, we investigated the role of CD43 in leukocyte-endothelial cell interactions within the cremasteric microcirculation under flow conditions. Our studies demonstrated significantly enhanced leukocyte rolling and adhesion after chemotactic stimuli in CD43(-/-) mice compared with wild type mice. Using an in vitro flow chamber, we established that the enhanced rolling interactions of CD43(-/-) leukocytes, primarily neutrophils, were also observed using immobilized E-selectin as a substrate, suggesting that passive processes related to steric hindrance or charge repulsion were likely mechanisms. Despite increased adhesion and rolling interactions by CD43(-/-) leukocytes, we uncovered a previously unrecognized impairment of CD43(-/-) leukocytes to infiltrate tissues. Oyster glycogen-induced neutrophil and monocyte infiltration into the peritoneum was significantly reduced in CD43(-/-) mice. In response to platelet activating factor, CD43(-/-) leukocytes were impaired in their ability to emigrate out of the vasculature. These results suggest that leukocyte CD43 has a dual function in leukocyte-endothelial interactions. In addition to its role as a passive nonspecific functional barrier, CD43 also facilitates emigration of leukocytes into tissues.