Polarized Ends of Human Macula Densa Cells: Ultrastructural Investigation and Morphofunctional Correlations

Abstract

The morphology of the kidney macula densa (MD) has extensively been investigated in animals, whereas human studies are scanty. We studied the fine structure of human MD cells focusing on their apical and basal ends and correlating structure and function. The MD region was examined by transmission electron microscopy in six renal biopsies from patients with kidney disease. Ultrastructural analysis of MD cells was performed on serial sections. MD cells show two polarized ends. The apical portion is characterized by a single, immotile cilium associated with microvilli; apically, cells are joined by adhering junctions. In the basal portion, the cytoplasm contains small, dense granules and numerous, irregular cytoplasmic projections extending to the adjacent extraglomerular mesangium. The projections often contain small, dense granules. A reticulated basement membrane around MD cells separates them from the extraglomerular mesangium. Although the fact that tissue specimens came from patients with kidney disease mandates extreme caution, ultrastructural examination confirmed that MD cells have sensory features due to the presence of the primary cilium, that they are connected by apical adhering junctions forming a barrier that separates the tubular flow from the interstitium, and that they present numerous basal interdigitations surrounded by a reticulated basement membrane. Conceivably, the latter two features are related to the functional activity of the MD. The small, dense granules in the basal cytoplasm and in cytoplasmic projections are likely related to the paracrine function of MD cells. Anat Rec, 301:922-931, 2018. © 2017 Wiley Periodicals, Inc.

Normal human macula densa morphology and cell turnover: A histological, ultrastructural, and immunohistochemical investigation

“…The present ultrastructural data confirm our earlier findings reported in MD tissue from patients with glomerulonephritis (Cangiotti et al, 2018). In particular, they confirm that these cells are characterized by a dual differentiation due to the presence of two functionally different compartments.…”

“…The ultrastructural examination demonstrated that MD cells from healthy tissue are identical to those found in the glomerulonephritis patients that we described in a previous paper (Cangiotti et al, 2018) (Figure 2). In the present material, MD cells showed two polarized ends: the apical end was endowed with a primary cilium, whereas the basolateral end showed morphological features of a paracrine secretory cell.…”

“…MD cells were easily identified in semithin sections by their morphological features, namely, they were arranged in a half‐circle, forming a plaque around the lumen of the DT, and showed palisade nuclei and a poorly developed lateral cytoplasm, which resulted in a greater cell density compared with neighboring tubular cells (Figure 1) (Cangiotti et al, 2018). Detection of the extraglomerular mesangium (with or without afferent and efferent arterioles) between the MD and the glomerulus also helped in the identification.…”

“…Most morphological MD studies have been performed in animals (Barajas, 1979; Barajas and Latta, 1963; Latta and Maunsbach, 1962; Rhodin, 1974; Sikri and Foster, 1981; Sottiurai and Malvin, 1972), while human studies are rare (Barajas, 1979; Tisher et al, 1968). In a recent paper, we began to study the fine structure of human MD cells, especially their apical and basal ends, and tried to establish structure–function relationships (Cangiotti et al, 2018). Although those findings have to be taken cautiously in the light of being inferred from kidney biopsies of glomerulonephritis patients, ultrastructural examination showed that MD cells (a) have sensory features related to the presence of the primary cilium, (b) are connected each other by mechanical apical junctions which form a barrier that separates the tubular flow from the interstitium, and (c) display numerous interdigitations at the basal end, which are surrounded by a thin reticulated basement membrane.…”

“…The present work aimed to collect quantitative data on the MD (e.g., size, number of layers, and number of cells) and to examine its ultrastructure in healthy tissue, to overcome the limitations of our previous study (Cangiotti et al, 2018). We demonstrated that the MD is a monolayer cap where 35–40 small, highly differentiated cells are arranged in rows.…”