Abstract
ObjectiveActivated mast cells in atherosclerotic lesions degranulate and release bioactive compounds capable of regulating atherogenesis. Here we examined the ability of activated human primary mast cells to regulate the expression of the major scavenger receptors in cultured human primary monocyte-derived macrophages (HMDMs).ResultsComponents released by immunologically activated human primary mast cells induced a transient expression of lectin-like oxidized LDL receptor (LOX-1) mRNA in HMDMs, while the expression of two other scavenger receptors, MSR1 and CD36, remained unaffected. The LOX-1-inducing secretory components were identified as histamine, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta (TGF-β1), which exhibited a synergistic effect on LOX-1 mRNA expression. Histamine induced a transient expression of LOX-1 protein. Mast cell –induced increase in LOX-1 expression was not associated with increased uptake of oxidized LDL by the macrophages.ConclusionsMast cell-derived histamine, TNF-α, and TGF-β1 act in concert to induce a transient increase in LOX-1 expression in human primary monocyte-derived macrophages. The LOX-1-inducing activity potentially endows mast cells a hitherto unrecognized role in the regulation of innate immune reactions in atherogenesis.
Highlights
Atherosclerosis is a disease with multifactorial etiology
The results indicated that the releasate collected from activated LAD2 mast cells and the pooled releasate collected from activated primary mast cells contained the following concentrations of components, respectively: histamine 0.7 and 7.4 mM; tumor necrosis factor alpha (TNF-a) 0 and 20 pg/ml; transforming growth factor beta-1 (TGF-b1) 116 and 87 pg/ml; of IL1-a 3.7 and 0 pg/ml
We report that immunologically activated human mast cells release compounds acting as potent inducers of LOX-1 mRNA expression in human primary monocyte-derived macrophages (MDM), while the expression of two other major macrophage scavenger receptors MSR1 and CD36 remained unaffected
Summary
Atherosclerosis is a disease with multifactorial etiology. A complex interplay between dyslipidemia, inflammation, coagulation, fibrinolysis, and endothelial dysfunction is involved in the pathophysiology of the disease. A key event in the formation of atherosclerotic plaques is transformation of macrophages into foam cells. This process is mediated by scavenger receptors (SRs), which enable internalization of modified low-density lipoprotein (LDL) particles, of oxidized LDL (oxLDL) [9]. CD36 accounts for approximately 40% of the oxLDL uptake [11]. In addition to CD36 and MSR1, a third important SR, oxidized low density lipoprotein (lectin-like) receptor 1 OLR1) has been shown to promote macrophage foam cell formation [12]
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