Neutrophils from MMP-9- or neutrophil elastase-deficient mice show no defect in transendothelial migration under flow in vitro.
Recent evidence has suggested a role for neutrophil proteases during certain inflammatory responses. We demonstrated previously that neutrophil proteases can degrade components of the adherens junctions during neutrophil-endothelial adhesion. We tested the hypothesis that degradation of VE-cadherin at lateral junctions by elastase or MMP-9 facilitates neutrophil transendothelial migration. Neutrophils from MMP-9 or elastase null mice and strain-matched control mice expressed high levels of LFA-1, Mac-1, and L-selectin on their cell surface. Under flow conditions, wild-type and deficient neutrophils rolled, arrested, and transmigrated activated murine endothelium. There was no difference in the total numbers of interacting neutrophils or in the percentage of transmigrated cells. In addition, deficient neutrophils remained capable of degrading murine endothelial VE-cadherin. These results indicate that although neutrophil proteases may play a role in the acute inflammatory response, neutrophil elastase or MMP-9 is not essential for neutrophil transendothelial migration in this murine system.
Allport
Jennifer R
JR
Vascular Research Division, Department of Pathology, Brigham & Women's Hospital and Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA.
Lim
Yaw-Chyn
YC
Shipley
J Michael
JM
Senior
Robert M
RM
Shapiro
Steven D
SD
Matsuyoshi
Norihisa
N
Vestweber
Dietmar
D
Luscinskas
Francis W
FW
D000818:Animals; D015703:Antigens, CD; D015415:Biomarkers / Q000032:analysis; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis; D002465:Cell Movement; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000276:immunology; D019272:Leukocyte Elastase / Q000235:genetics / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009504:Neutrophils / Q000201:enzymology* / Q000276:immunology; D000099152:Cadherin 5
D015703:Antigens, CD; D015415:Biomarkers; D015820:Cadherins; D015815:Cell Adhesion Molecules; D016207:Cytokines; D019272:Leukocyte Elastase; D020780:Matrix Metalloproteinase 9; D000099152:Cadherin 5