Fibronectin augments monocyte adhesion to low-density lipoprotein-stimulated mesangial cells.
BACKGROUND
Glomerular monocyte infiltration is an early feature of lipid-mediated renal injury in animal models. Interactions between mesangial and infiltrating mononuclear cells may contribute to the development of glomerular scarring.


METHODS
Adherence of U-937 monocytes to low-density lipoprotein (LDL)- or tumor necrosis factor alpha (TNFalpha)-prestimulated human mesangial cells was assessed by colorimetry of nuclear staining with crystal violet. Blocking antibodies were added to examine the mechanisms of binding. Adhesion molecule expression and fibronectin synthesis were measured by ELISA.


RESULTS
Preincubation of mesangial cells for 24 hours with LDL (100 micrograms/ml) or mildly oxidized (minimally modified) LDL (MM-LDL) increased monocyte adhesion by 207% and 240%, respectively, compared with control nonstimulated cells (100%). TNFalpha (100 U/ml) enhanced binding by 335% and up-regulated intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression by 505% and 179%, respectively, as compared with MM-LDL (120% and 116%) and LDL, which had no effect. Blocking antibodies to these adhesion molecules inhibited monocyte binding to TNFalpha- and, to a lesser extent, MM-LDL-primed mesangial cells, but had no effect after LDL pretreatment. In contrast to TNFalpha, MM-LDL and LDL increased mesangial cell-associated fibronectin, whereas antibodies to fibronectin inhibited monocyte binding to lipoprotein-stimulated but not TNFalpha-stimulated cells.


CONCLUSIONS
Although enhanced monocyte adhesion to TNFalpha- and, to a lesser extent, MM-LDL-stimulated mesangial cells is mediated by changes in ICAM-1 and VCAM-1 expression, both LDL and MM-LDL promote similar cellular interactions as a result of increased fibronectin production.
Chana
R S
RS
Department of Nephrology, University Hospital NHS Trust, Queen Elizabeth Hospital, Birmingham, England, United Kingdom.
Wheeler
D C
DC
D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D005353:Fibronectins / Q000096:biosynthesis / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D005353:Fibronectins; D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1