Macrophages in Kidney Injury and Repair

Abstract

Macrophages (Mφs) are monocyte-derived tissue effector cells from hematopoietic stem cells in bone marrow via circulation. Their expansion in tissues can either be due to local proliferation of resident cells or infiltration from the circulation, depending on the stimulus (1-3). Beyond their traditional role in protecting the host from invading pathogens, Mφs have been shown to play expansive roles as regulators of development, tissue homeostasis, remodeling, and repair (4). Although the key role of Mφs in kidney repair after injury is gaining considerable appreciation, along with neutrophils, Mφs have a reputation of being leukocytes which drive tissue injury and fibrosis in immunological and chronic inflammatory kidney diseases (5-8). During disease, Mφs expand even in the absence of pathogens, and disperse after repair or recovery (8). However, a large population of Mφs persists after expansion in chronic progressive kidney disease (3, 9). In many human kidney biopsy studies, Mφs have been found in large numbers in both acute diseases such as post-streptococcal glomerulonephritis (GN), anti-neutrophil cytoplasmic antibody (ANCA) associated GN, or in chronic diseases such as IgA nephropathy or lupus nephritis, and also in acute and chronic kidney transplant disease (10-17). Many studies have shown that the tissue of Mφs are in fact not merely passive bystander cells, but are activated and involved in the pathogenesis of kidney diseases. These observations hold true not only in immunological kidney diseases such as GN but also in nonimmunological diseases, such as diabetic nephropathy, ischemic/vascular kidney disease, and all forms of chronic kidney disease (18-27). In all of these diseases, the cell numbers and activation status of Mφs have been reported to correlate positively with disease severities (28-32).