Renal microenvironments and macrophage phenotypes determine progression or resolution of renal inflammation and fibrosis.

Abstract

Chronic kidney disease involves renal inflammation, interstitial fibrosis, and tubular and vascular atrophy. Macrophages seem to foster all of these histomorphological abnormalities, but their specific contributions remain controversial. Recruited monocytes differentiate into different tissue macrophage phenotypes, but current classifications are largely based on in vitro studies that do not adequately mirror tissue environments in vivo. To overcome this limitation, we propose to classify tissue macrophages according to their predominant roles in the phases of wound healing tissue environments, that is, inflammation, epithelial healing, mesenchymal healing, and fibrolysis. In this review, we discuss the evidence on respective macrophage phenotypes in renal pathology. This view sheds light on several aspects of renal remodeling in kidney disease: (1) renal infection or cell necrosis induces proinflammatory 'M1' macrophages that exacerbate renal cell damage, (2) uptake of apoptotic cells induces anti-inflammatory 'M2c/suppressor' macrophages that promote epithelial and vascular repair, (3) insufficient vascular and epithelial healing despite abundant growth factor secretion promotes profibrotic 'M2a/wound healing' macrophages that accelerate fibrogenesis, and (4) theoretically, fibrolytic macrophages should exist and await investigation.