Lipoprotein activated macrophages in co-culture with mesangial and endothelial cells: nitric oxide and tissue injury.
Experiments were conducted to test the hypothesis that VLDL induced excess NO in macrophages may be the mechanism of tissue injury that explains the risk associated with VLDL towards the development of cardiovascular and renal diseases. VLDL activated macrophages were co-cultured with endothelial and mesangial cells. The results showed 59-63 fold higher NO production in VLDL activated macrophages compared to the unactivated macrophages. Nitric oxide production was further potentiated by an additional four fold (241 fold) in VLDL activated macrophage/mesangial cell co-cultures. In co-cultures of VLDL activated macrophages/endothelial cells, NO production was 47 fold higher than the corresponding controls. Cell injury as measured by lactate dehydrogenase activity in cell culture supernatant was elevated in co-cultures of VLDL activated macrophage and mesangial or endothelial cells. Endothelial cells were more susceptible to nitric oxide mediated injury than mesangial cells. On the other hand, low density lipoprotein (LDL) activated macrophages did not generate significant NO or exert toxicity. These results provide support for the mechanism by which VLDL can cause tissue injury and highlights increased nitric oxide production due to the interaction between VLDL activated macrophages and mesangial cells.
Mohan
P F
PF
Department of Pathology, University of Mississippi Medical Center, Jackson 39216, USA.
D000818:Animals; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D005920:Glomerular Mesangium / Q000502:physiology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000494:pharmacology*; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D008079:Lipoproteins, VLDL; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase