Part of CD68+ macrophages in the clearence of apoptotic bodies in human metanephros.

Abstract

According to recent research on mice, less on human material, cells responsible for clearing apoptotic cells away during development are, besides non-professional phagocytes, also tissue-fixed macrophages. The aim of our work was the determination of macrophage role in the phagocytosis of apoptotic bodies in neogenous zone of human metanephros. Histologicaly normal kidneys were collected from embryos and fetuses ranging from the 8th-28th week of IUD. These tissues were routinely processed. In the first step we detected CD68+ cells by means of standard indirect three-step immunohistochemical method having used MAb NCL-CD68-KP1 (macrophage marker) to find out whether such cells are actually present. In the second step tissue sections were labelled by double-staining principle (TUNEL technique for the detection of apoptosis and above mentioned macrophage marker) to judge co-localization of these two items. The slides were observed by using immersion objective and the amount of apoptotic cells was expressed in percents. CD68+ macrophages appeared dispersely as single cells or small groups in all the ages studied. According to our results, CD68+ macrophages phagocytose 37-75% of apoptotic cells present in neogenous zone and the number of engulfed apoptotic cells increases in the 12th week of the IUD, i.e. in the early fetal period and later it merely fluctuates.

Role of mitotic, pro-apoptotic and anti-apoptotic factors in human kidney development

“…In the 5th developmental week, bcl-2 positive cells appeared in the metanephros, later on increasing in the nephrons, particularly in less mature forms, as previously shown by Prochazkova et al [36]. Throughout the developmental stages investigated, bcl-2 positive cells were hardly or not at all detectable in derivatives of the ureteric bud, as earlier described in human tissue [24][25][26]36]. Experiments with bcl-2 deficient mice showed kidney abnormalities, including hypoplasia with fulminant apoptosis within the metanephric mesenchyme [15,16].…”

“…Only few studies of their expression pattern in the mesonephros and metanephros have been performed in human embryos [13,14], some of them done on developmental stages different from ours [24][25][26].…”

The Origins and Functions of Tissue-Resident Macrophages in Kidney Development

“…During renal development, efferocytosis is carried out by kidney macrophages (Camp and Martin, 1996 ; Erdösová et al, 2002 ). “Find me” chemokine signals and “eat me” cell surface signals that are expressed by dying cells attract macrophages to phagocytose them (Truman et al, 2008 ; Nagata et al, 2010 ), resulting in the degradation of their cellular components (A-Gonzalez and Hidalgo, 2014 ).…”

Clearance of dying cells and autoimmunity

“…Apart from translocation of PS (or oxPS), apoptotic cells are characterised by surface exposure of oxidised low-density lipoproteins (oxLDL) [35] recognised by diverse scavenger receptors: SR-A (class A macrophage scavenger receptor) [36], lectin-like oxLDLreceptor-1 (LOX-1) [37], CD-68 [38] and CD36 [39]. Another class of rather poorly characterised "eat me" signals are sites binding TSP-1 [40], complement proteins C1q or C3b/bi [41] or collectins like mannose binding lectin (MBL) or lung surfactant proteins-A and -D (SP-A and SP-D) [42].…”