Differential effects of histamine and thrombin on endothelial barrier function through actin-myosin tension.
We compared temporal changes in isometric tension in cultured human umbilical vein endothelial cells inoculated on a polymerized collagen membrane with changes in cell-cell and cell-matrix adhesion derived by a mathematical model of transendothelial cell resistance. Thrombin and histamine disrupt barrier function by targeting a greater loss in cell-cell adhesion, which preceded losses in overall transendothelial resistance. There were minor losses in cell-matrix adhesion, which was temporally slower than the decline in the overall transendothelial resistance. In contrast, thrombin and histamine restored barrier function by initiating a restoration of cell-matrix adhesion, which occurred before an increase in overall transendothelial resistance. Thrombin mediated a second and slower decline in cell-cell adhesion, which was not observed in histamine-treated cells. This decline in cell-cell adhesion temporally correlated with expressed maximal levels of tension development, suggesting that actin-myosin contraction directly strains cell-cell adhesion sites. Pretreatment of cells with ML-7 mediated more rapid recovery of cell-cell adhesion and had no effect on cell-matrix adhesion. Taken together, expression of actin-myosin contraction affects the restoration of barrier function by straining cell-cell adhesion sites.
Moy
Alan B
AB
Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA. alan-moy@uiowa.edu
Blackwell
Ken
K
Kamath
Anant
A
D000199:Actins / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D009218:Myosins / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology*; D014471:Umbilical Veins
D000199:Actins; D006632:Histamine; D013917:Thrombin; D009218:Myosins