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Mesangial matrix‐activated mononuclear cells express functional scavenger receptors and accumulate intracellular lipid
Author(s) -
Rahman Enam,
Chana Ravinder S.,
Ruan Xiong Z.,
Powis Stephen H.,
Varghese Zac,
Wheeler David C.
Publication year - 2004
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/j.0959-9673.2004.369ah.x
Subject(s) - scavenger receptor , mesangial cell , monocyte , receptor , foam cell , chemistry , mesangium , peripheral blood mononuclear cell , peroxisome proliferator activated receptor , microbiology and biotechnology , lipoprotein , macrophage , biology , endocrinology , biochemistry , in vitro , glomerulonephritis , immunology , cholesterol , kidney
Monocyte recruitment into the mesangium and foam cell formation are recognized features of glomerular injury. External signals encountered by these infiltrating cells may determine their behaviour and thereby potentially influence disease outcomes. Our previous studies indicate that activation of monocytes by mesangial matrix stimulates the production of a variety of mediators including inflammatory cytokines and matrix degrading enzymes. Methods Using expression of peroxisome proliferator activator receptor‐γ (PPAR‐γ) and scavenger receptor (ScR) as differentiation markers, we examined whether matrix activation was associated with the expression of monocyte characteristics usually associated with a macrophage phenotype. THP‐1 mononuclear cells were incubated for 7 days with 500 µg/ml solublized matrix extracted from cultured human mesangial cells. Results Using phorbol methyl ester (PMA) (125 nm) and albumin (500 µg/ml) as positive and negative controls, respectively, we demonstrated that matrix activation of monocytes led to intracellular lipid accumulation as demonstrated by oil red O staining. Matrix activation was also associated with a concentration‐dependent increase in the expression of both ScR and PPAR‐γ mRNA and a corresponding increase in PPAR‐γ protein expression on Western blotting. The presence of functional ScR was confirmed using FACS analysis in which incubation of matrix‐activated monocytes with Dil‐labelled acetylated low‐density lipoprotein (LDL) led to an increase in mean fluorescent intensity of 373% ( P < 0.001) as compared to albumin (100%) and PMA (423%). This could be inhibited by addition of excess unlabelled ligand, suggesting specific binding to the ScR. Furthermore, incubation of LDL with mesangial matrix in the absence of cells led to enhanced electrophoretic mobility of recovered lipoprotein on agarose gel. A similar shift was seen when LDL was incubated with Cu 2+ , a powerful lipoprotein oxidant. Discussion These results demonstrate that interactions with mesangial matrix induce expression of monocyte characteristics associated with a macrophage phenotype and promote oxidation of LDL, thereby converting it to an ScR ligand. Such observations may help to explain foam cell formation in the mesangium in the context of glomerular disease.