Intercellular adhesion molecule-1, intercellular adhesion molecule-3, and leukocyte integrins in leukocyte accumulation in membranoproliferative glomerulonephritis type i

Reverse cholesterol transport (RCT) is considered as the most important antiatherogenic role of high-density lipoproteins (HDL), but interventions based on RCT have failed to reduce the risk of coronary heart disease. In contrast to RCT, important evidence suggests that HDL deliver lipids to peripheral cells. Therefore, in this paper, we investigated whether HDL could improve endothelial function by delivering lipids to the cells. Internalization kinetics using cholesterol and apolipoprotein (apo) AI fluorescent double-labeled reconstituted HDL (rHDL), and human dermal microvascular endothelial cells-1 (HMEC-1) showed a fast cholesterol influx (10 min) and a slower HDL protein internalization as determined by confocal microscopy and flow cytometry. Sphingomyelin kinetics overlapped that of apo AI, indicating that only cholesterol became dissociated from rHDL during internalization. rHDL apo AI internalization was scavenger receptor class B type I (SR-BI)-dependent, whereas HDL cholesterol influx was independent of SR-BI and was not completely inhibited by the presence of low-density lipoproteins (LDL). HDL sphingomyelin was fundamental for intercellular adhesion molecule-1 (ICAM-1) downregulation in HMEC-1. However, vascular cell adhesion protein-1 (VCAM-1) was not inhibited by rHDL, suggesting that components such as apolipoproteins other than apo AI participate in HDL’s regulation of this adhesion molecule. rHDL also induced endothelial nitric oxide synthase eNOS S1177 phosphorylation in HMEC-1 but only when the particle contained sphingomyelin. In conclusion, the internalization of HDL implies the dissociation of lipoprotein components and a SR-BI-independent fast delivery of cholesterol to endothelial cells. HDL internalization had functional implications that were mainly dependent on sphingomyelin. These results suggest a new role of HDL as lipid vectors to the cells, which could be congruent with the antiatherogenic properties of these lipoproteins.

Download Full-text

dsRNA activation of endothelin-1 and markers of vascular activation in endothelial cells and fibroblasts

Annals of the Rheumatic Diseases ◽

10.1136/ard.2010.132464 ◽

2010 ◽

Vol 70 (3) ◽

pp. 544-550 ◽

Cited By ~ 27

Author(s):

Giuseppina Farina ◽

Michael York ◽

Cindy Collins ◽

Robert Lafyatis

Keyword(s):

Endothelial Cells ◽

Adhesion Molecule ◽

Intercellular Adhesion ◽

Dermal Fibroblasts ◽

Innate Immune ◽

Poly I:C ◽

Intercellular Adhesion Molecule ◽

Type I ◽

Intercellular Adhesion Molecule 1 ◽

Endothelin 1

BackgroundIn patients with systemic sclerosis (SSc), the relationship between innate immune activation, represented by increased expression of interferon (IFN)-regulated genes, and vascular injury/activation, manifest by increased endothelin-1 (ET-1), endothelin converting enzyme-1 (ECE1) and intercellular adhesion molecule-1, is uncertain.ObjectiveTo investigate the potential roles of innate immune ligands in both these pathogenic pathways.MethodsThe effect of known Toll-like receptor (TLR) ligands was tested in vitro on dermal microvascular and pulmonary arterial endothelial cells, and on dermal fibroblasts cultured from healthy controls and patients with SSc. To test the effect of double-stranded RNA (dsRNA) on vascular activation/injury in vivo, polyinosinic/polycytidylic acid (poly(I:C)) was administered continuously over 7 days by subcutaneous osmotic pump.ResultsdsRNA/poly(I:C), but not other TLR ligands, highly stimulated ET-1 protein and mRNA (EDN1), as well as intercellular adhesion molecule-1 (ICAM-1) and IFN-regulated MX2, by endothelial cells and dermal fibroblasts. Poly(I:C) induced EDN1, ECE1, and ICAM-1 mRNA expression in poly(I:C) treated skin. Poly(I:C)-induced EDN1, ECE1 and MX2 was not blocked in mice with the type I IFN receptor deleted. However, poly(I:C)-induced EDN1 and ECE1, but not poly(I:C)-induced ICAM-1 expression was blocked in mice with the TLR3 signalling protein TRIF/TICAM-1 deleted.ConclusionTogether these data show that the dsRNA can regulate genes associated with vascular activation, as seen in SSc, that type I IFNs do not mediate these effects, and that EDN1 and ECE1 but not ICAM-1 activation is mediated by TLR3.

Download Full-text

Renal expression of intercellular adhesion molecule-1 in different forms of glomerulonephritis

Clinical Science ◽

10.1042/cs0810477 ◽

1991 ◽

Vol 81 (s25) ◽

pp. 477-481 ◽

Cited By ~ 66

Author(s):

K. Lhotta ◽

H. P. Neumayer ◽

M. Joannidis ◽

D. Geissler ◽

P. KöNig

Keyword(s):

Iga Nephropathy ◽

Focal Segmental Glomerulosclerosis ◽

Adhesion Molecule ◽

Membranoproliferative Glomerulonephritis ◽

Rapidly Progressive Glomerulonephritis ◽

Intercellular Adhesion ◽

Intercellular Adhesion Molecule ◽

Intercellular Adhesion Molecule 1 ◽

Segmental Glomerulosclerosis ◽

Mesangioproliferative Glomerulonephritis

1. Expression of intercellular adhesion molecule-1 was investigated in five normal kidneys and 47 renal biopsies with the use of monoclonal antibody 7F7 and immunoperoxidase staining. 2. In the normal kidney, intercellular adhesion molecule-1 was expressed on endothelial cells of glomerular and peritubular capillaries, on Bowman's capsule, on some interstitial cells and weakly in the mesangium. 3. Increased glomerular staining was detected in early cases of rapidly progressing glomerulonephritis (5/8) and in some cases of non-IgA mesangioproliferative glomerulonephritis (5/9), IgA nephropathy (3/5), Henoch-Schoenlein purpura (2/2), lupus nephritis (5/6) and focal segmental glomerulosclerosis (1/3). A decrease in intercellular adhesion molecule-1 expression was noted in advanced rapidly progressive glomerulonephritis (3/8), two cases of membraneous nephropathy, one severe mesangioproliferative glomerulonephritis biopsy, the two membranoproliferative glomerulonephritis biopsies and in sclerotic loops in focal segmental glomerulosclerosis. 4. Expression de novo on tubular epithelial cells occurred in rapidly progressive glomerulonephritis, in membranoproliferative glomerulonephritis, and to a lesser extent in some cases of membranous nephropathy, minimal change disease, IgA nephropathy, focal segmental glomerulosclerosis, a severe case of mesangioproliferative glomerulonephritis and in the mixed essential cryoglobulinaemia case. In 63% of positive tubuli, intraluminal cells which expressed CD18, the common β-chain of leucocyte-function-associated antigen-1, Mac-1 and p150,95, were present. 5. Intercellular adhesion molecule-1 was also found on the majority (59%) of infiltrating mononuclear cells in all forms of glomerulonephritis.

Download Full-text