Stabilin-1 expression defines a subset of macrophages that mediate tissue homeostasis and prevent fibrosis in chronic liver injury

Abstract

Significance Organ fibrosis is a major cause of global morbidity and mortality. It is driven by chronic inflammation and associated oxidative stress with depletion of cellular antioxidant defenses. We demonstrate a pathway in which the evolutionarily conserved receptor stabilin-1 on tissue-infiltrating macrophages provides a second-line defense to prevent tissue damage from oxidative stress. Stabilin-1 + monocytes take up malondialdehyde-LDL (MDA-LDL), a major product of oxidative lipid peroxidation, to form ceroid-laden macrophages. Through the uptake of MDA-LDL, stabilin-1 suppresses production of the profibrogenic chemokine CCL3 and prevents excessive collagen deposition in experimental models of liver fibrosis. We propose that macrophage stabilin-1 is a critical defense against oxidative tissue damage and thereby maintains tissue homeostasis.