Immunohistochemical detection of macrophage‐derived foam cells and macrophage colony‐stimulating factor in pulmonary atherogenesis of cholesterol‐fed rabbits

Abstract

In order to investigate the role of monocyte/macrophages and their relationship to the expression of macrophage colony-stimulating factor (MCSF) in pulmonary atherosclerosis, lungs were excised from rabbits that had been fed for 60 and 90 days on a diet containing 0.5% cholesterol. In the lungs, fatty streaks and elevated foam cell lesions predominated in the large or medium-sized elastic pulmonary arteries, while massive accumulation of foam cells in the intima of muscular arteries produced marked luminal narrowing and nearly complete occlusion. In these lesions, most of the foam cells were reactive with RbM2, a monoclonal antibody (mAb) against rabbit macrophages, while smooth muscle cell-derived foam cells were detected by mAb against smooth muscle actin in the deeper area of elevated foam cell lesions of elastic arteries. Ultrastructural observation confirmed the presence of monocytes in the intima, their differentiation into macrophages, and their transformation into foam cells in the atherosclerotic lesions. Immunohistochemical expression of MCSF was demonstrated in the endothelial cells, smooth muscle cells and foam cells. A minor macrophage-derived foam cell population was demonstrated to possess a proliferative capacity. These data suggest that MCSF is involved in the differentiation of monocytes into macrophages, their transformation into foam cells, and their proliferation during pulmonary atherogenesis.

Up-regulation of macrophage colony-stimulating factor (M-CSF) and migration inhibitory factor (MIF) expression and monocyte recruitment during lipid-induced glomerular injury in the exogenous hypercholesterolaemic (ExHC) rat

“…Up-regulation of M-CSF expression by LDL operates through activation of the nuclear transcription factor NF-kB [28], a factor which induces the expression of a number of molecules involved in the inflammatory response, such as leucocyte adhesion molecules, which are also rapidly upregulated in ExHC rats fed an HCD [22]. Local production of M-CSF has been described in vascular atherosclerotic lesions [9][10][11], and M-CSF may contribute to foam cell formation by upregulating monocyte expression of the LDL receptor and lipid metabolism [29][30][31]. In addition, genetic studies in mice have demonstrated a key role for M-CSF and its effects upon macrophage development and function in the pathogenesis of atherosclerosis [32].…”

“…Although M-CSF has not been studied in lipid-induced renal injury, several studies point to a role for this molecule in monocyte recruitment in this form of renal injury. Local M-CSF expression and macrophage accumulation have been demonstrated in vascular atherosclerotic lesions [9][10][11]. Increased glomerular M-CSF expression has been implicated in glomerular macrophage accumulation and the development of glomerular injury in murine lupus nephritis [12].…”

Cathepsin S generates soluble CX3CL1 (fractalkine) in vascular smooth muscle cells

“…Circulating monocytes are precursors of the lipid-laden macrophages (foam cells) that contribute to inflammation in early and advanced atherosclerotic lesions (Ruan et al, 1995). However, it is not known which proteases are involved in CX3CL1 shedding from the VSMC surface.…”

Alterations of lung structure in experimental diabetes, and diabetes associated with hyperlipidaemia in hamsters

“…More recently, increased levels of cholesterol content in the lungs [20], systemic induction of 15-lipoxygenase activity [21], and massive accumulation of foam cells in the intima of lung muscular arteries during pulmonary atherogenesis [22] were reported.…”