Low density lipoproteins transfer bacterial lipopolysaccharides across endothelial monolayers in a biologically active form.
Rabbit aortic endothelial cells (RAECs) were grown on micropore filters in a device that allowed in situ determination of transendothelial electrical resistance (TEER). Incubation of confluent RAEC monolayers with 2 ng.ml-1 of bacterial LPS for 3 h did not change the protein content or the number of cells on the filters, but resulted in a marked decline in TEER (from 14.1 +/- 0.9 to 5.1 +/- 0.6 omega.cm2) and a significant increase in LDL transport across the monolayers (from 154 +/- 13 to 456 +/- 41 ng. h-1 per cm2). In contrast, exposure of RAEC monolayers for 3 d to as much as 5 micrograms.ml-1 of LPS complexed to LDL (LPS-LDL) did not alter the TEER or LDL transport. LPS-LDL was transported across the monolayers at the same rate as LDL. While microgram quantities of LPS complexed to LDL did not disrupt the integrity of the endothelial monolayer, incubation of RAECs with transported LPS-LDL at concentrations of 25-100 ng LPS.ml-1 resulted in a two- to ninefold increase in the secretion of monocyte chemotactic activity by these cells. Incubation of rabbit aortic smooth muscle cells with transported LPS-LDL at concentrations of 25-100 ng LPS.ml-1 resulted in a two- to threefold increase in the secretion of monocyte chemotactic activity. We propose that LDL protects endothelial cells from the acute toxicity of LPS but the resulting complexes are transported across the endothelium in a biologically active form that can initiate an inflammatory response.
Navab
M
M
Department of Medicine, School of Medicine, University of California, Los Angeles 90024.
Hough
G P
GP
Van Lenten
B J
BJ
Berliner
J A
JA
Fogelman
A M
AM
D000818:Animals; D001692:Biological Transport; D002634:Chemotaxis, Leukocyte; D004553:Electric Conductivity; D004730:Endothelium, Vascular / Q000378:metabolism*; D004731:Endotoxins / Q000378:metabolism; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009000:Monocytes / Q000502:physiology; D011817:Rabbits
D004731:Endotoxins; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL