Involvement of adhesion molecules in human monocyte adhesion to and transmigration through endothelial cells in vitro.
Although the accumulation of monocyte-derived foam cells in the subendothelium is a key step in early atherogenesis, the mechanism responsible for monocyte adhesion to and subsequent transmigration through endothelial cells (ECs) has not been defined fully. We investigated the kinetics and the role played by adhesion molecules in the adhesion and transmigration of human monocytes using an in vitro three-dimensional model system comprising ECs cultured on collagen gels. Monocyte adhesion to untreated EC layers increased with time, reached a maximum after 3 h, and then declined. Monocyte transmigration through untreated EC layers also increased with time and reached a plateau after 3-4 h. Prestimulation of ECs with interleukin-1 beta (IL-1 beta; 25 U/ml) for 4 h enhanced monocyte adhesion (40.7 +/- 1.4%) and transmigration (37.9 +/- 1.6%) significantly compared with the value for untreated EC layers. In unstimulated EC layers, anti-leukocyte function-associated antigen-1 (LFA-1) plus anti-intercellular adhesion molecule-1 (ICAM-1) monoclonal antibodies (mAbs) inhibited monocyte adhesion and transmigration significantly by 19% and 20%, respectively, whereas anti-very late antigen-4 (VLA-4) plus anti-vascular cell adhesion molecule-1 (VCAM-1) mAbs did not. In IL-1 beta-stimulated EC layers, anti-LFA 1 plus anti-ICAM-1 mAbs inhibited the adhesion and transmigration by 32% and 30%, respectively and anti-VLA-4 plus anti-VCAM-1 mAbs did so by 18% and 27%, respectively. These results suggest that the monocyte-EC interaction in unstimulated ECs is mediated, in part, by the LFA-1-ICAM-1 pathway and in IL-1 beta-stimulated ECs, in part, by both LFA-1-ICAM-1 and VLA-4-VCAM-1 pathways.
Takahashi
M
M
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Ikeda
U
U
Masuyama
J
J
Kitagawa
S
S
Kasahara
T
T
Saito
M
M
Kano
S
S
Shimada
K
K
D000911:Antibodies, Monoclonal; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000494:pharmacology / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000494:pharmacology / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000494:pharmacology / Q000502:physiology; D009000:Monocytes / Q000502:physiology*; D016029:Receptors, Very Late Antigen / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D016029:Receptors, Very Late Antigen; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1