Shear stress inhibits adhesion of cultured mouse endothelial cells to lymphocytes by downregulating VCAM-1 expression.
Monolayers of endothelial cells (EC) cultured from mouse lymph nodes were exposed to controlled levels of shear stress (0-7.1 dyn/cm2) in a parallel plate flow chamber, and binding between the flow-loaded EC and mouse lymph node-derived lymphocytes was assayed. A large number of lymphocytes adhered to the stationary control EC, but in EC exposed to a shear stress of 1.5 dyn/cm2 for 6 h, the adhesion decreased to 68.8 +/- 12.8% (SD; n = 19) of control (n = 29, P < 0.001). The decrease in adhesion induced by flow loading was time and shear stress dependent and reversible. Treatment of stationary EC with a monoclonal antibody (MAb) to vascular cell adhesion molecule-1 (VCAM-1) reduced the adhesion to 70.6 +/- 11.5% (n = 19) of control (P < 0.001), whereas MAb to CD44 and to intercellular adhesion molecule-1 had no effect on it. Flow cytometric analysis revealed that the amount of VCAM-1 expressed on the cell surface was decreased to 48.5 +/- 15.8% (n = 6) of control by flow loading (P < 0.001). Flow loading experiments using two perfusates with different viscosities demonstrated that the decrease in VCAM-1 expression due to flow was shear stress rather than shear rate dependent. The detection of mRNA by reverse transcriptase-polymerase chain reaction showed that VCAM-1 mRNA levels were markedly depressed in EC exposed to flow loading.(ABSTRACT TRUNCATED AT 250 WORDS)
Ando
J
J
Department of Cardiovascular Biomechanics, Faculty of Medicine, University of Tokyo, Japan.
Tsuboi
H
H
Korenaga
R
R
Takada
Y
Y
Toyama-Sorimachi
N
N
Miyasaka
M
M
Kamiya
A
A
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D018960:Hyaluronan Receptors; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology*; D008214:Lymphocytes / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D013314:Stress, Mechanical; D019010:Vascular Cell Adhesion Molecule-1
D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D018960:Hyaluronan Receptors; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1