title: 4D intravital microscopy uncovers critical strain differences for the roles of PECAM and CD99 in leukocyte diapedesis.
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.
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Chicago, Illinois.
authors.forename: David P
authors.identifier: 0000-0002-7462-3898
authors.initials: DP
authors.lastname: Sullivan
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Watson
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Chicago, Illinois wamuller@northwestern.edu.
authors.forename: William A
authors.initials: WA
authors.lastname: Muller
mesh_terms: D000071443:12E7 Antigen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000009:Abdominal Muscles / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001485:Basement Membrane; D002448:Cell Adhesion; D003436:Croton Oil / Q000009:adverse effects; D003877:Dermatitis, Contact / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D003879:Dermatologic Agents / Q000009:adverse effects; D005434:Flow Cytometry; D000069416:Intravital Microscopy; D007962:Leukocytes / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009504:Neutrophils; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D057705:Transendothelial and Transepithelial Migration
chemical_list: D000071443:12E7 Antigen; D019138:Antibodies, Blocking; C522605:Cd99 protein, mouse; D003879:Dermatologic Agents; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D003436:Croton Oil
keywords: CD99; diapedesis; inflammation; intravital microscopy; platelet/endothelial cell adhesion molecule