Abstract
Leukocyte transendothelial migration (TEM) is an essential component of the inflammatory response. In vitro studies with human cells have demonstrated that platelet/endothelial cell adhesion molecule (PECAM) functions upstream of CD99 during TEM; however, results in vivo with mice have been apparently contradictory. In this study we use four-dimensional (4D) intravital microscopy to demonstrate that the site and order of function of PECAM and CD99 in vivo are dependent on the strain of mice. In FVB/n mice, PECAM functions upstream of CD99, as in human cells in vitro, and blocking antibodies against either molecule arrest neutrophils before they traverse the endothelium. However, in C57BL/6 mice, PECAM and CD99 appear to function at a different step, as the same antibodies arrest leukocyte migration through the endothelial basement membrane. These results are the first direct comparison of PECAM and CD99 function in different murine strains as well as the first demonstration of the sequential function of PECAM and CD99 in vivo.
| Original language | English (US) |
|---|---|
| Pages (from-to) | H621-H632 |
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 311 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 2016 |
Funding
This work was supported by National Heart, Lung, and Blood Institute Grants R01 HL-046849 and R37 HL-04774 to W. A. Muller and F30 HL-116100 to R. L. Watson and by the Northwestern University Flow Cytometry Core Facility, supported by National Cancer Institute Cancer Center Support Grant CA-060553. Publication costs for this article were paid in part by support from the Sydney and Bess Eisenberg Memorial Fund.
Keywords
- CD99
- Diapedesis
- Inflammation
- Intravital microscopy
- Platelet/endothelial cell adhesion molecule
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
- Physiology