Anat Embryol(1996) 193:303-318 9 Springer-Verlag 1996 Brigitte Kaissling 9 Ivan Hegyi 9 Johannes Lofting Michel Le Hir Morphology of interstitial cells in the healthy kidney Accepted: 6 December 1995 Abstract Renal interstitial cells play an important role in renal function and renal diseases. We describe the morphology of renal interstitial cells in the healthy kid- ney. We distinguish within the renal interstitium (1) renal fibroblasts and (2) cells of the immune system. Fibro- blasts are in the majority and constitute the scaffold of the kidney; they are interconnected by junctions, and are attached to tubules and vessels. Although the phenotype of fibroblasts shows some variation depending on their location in the kidney and on their functional stage, their recognition as fibroblasts is possible on account of struc- tural features. Among the cell types of the second group, antigen-presenting dendritic cells are the most abundant in in the peritubular interstitial spaces of healthy kid- neys. Their incidence is highest in the inner stripe of the outer medulla. They share some morphological features with fibroblasts but lack others - junctional complexes, morphologically defined connections with tubules and vessels, and the prominent layer of actin filaments under the plasma membrane - that are characteristic for fibro- blasts. Dendritic cells in healthy kidneys are morphologi- cally different from macrophages, which are character- ized by abundant primary and secondary lysosomes. In healthy kidneys macrophages are restricted to the con- nective tissue of the renal capsule and the pelvic wall, and to the periarterial connective tissue. Lympbocytes are rare in healthy kidneys. The distinction of cell types by morphology is supported by differences of membrane proteins. Among all interstitial cells in the renal cortex, fibroblasts alone exhibit ecto-5'-nucleotidase. Dendritic cells constitutively have a high abundance of MHC class II protein. Both proteins are mutually exclusive. Rat macrophages display the membrane antigen ED 2 and B. Kaissling(~) 9 I. Hegyi - J. Lofting AnatomischesInstitutder Universit~it Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland Tel.: ++41-1-257 53 40; Fax: ++41-1-257 5702; e-mail: bkaissl @ anatomie.unizh.ch M. Le Hir Institut ftir Toxikologie,Universit~it und ETH Zurich, Switzerland lymphocytes exhibit specific surface antigens, depending on their type and functional stage, e.g., CD4 or CD8. Key words Fibroblasts 9 Dendritic cells 9 Ecto-5'-nucleotidase 9 MHC class II Introduction The interstitium is involved in virtually all functions of the healthy kidney. A transit across the interstitial extra- cellular compartment is obligatory for all substances transported from tubules to blood and reciprocally, as well as for many regulatory substances from their site of production to their site of action (Lemley and Kriz 1991). The interstitial cells, besides taking part in the modeling of the extracellular matrix, play a role in the production of regulatory substances and in immune pro- cesses (Wolf and Neilson 1991; Fine et al. 1995). A spe- cific function of renal interstitial cells in the kidney cor- tex is the production of erythropoietin. A renaissance of interest in the renal tubulointerstitial compartment has occurred in recent years due to the growing awareness that the peritubular interstitium, even though its overall fractional volume is small (Lemley and Kriz 1991), plays a pivotal role in renal pathologies and constitutes a major factor determining the issue of renal failures (Bohle et al. 1990; Kuncio et al. 1991; Cameron 1992; Fine et al. 1995). The interest directed towards the interstitium is in striking contrast to the relatively slight knowledge about the morphological aspects of renal tu- bulointerstitium in healthy kidneys in vivo. The reasons for this discrepancy are in part due to technical prob- lems. The morphological study of the interstitium in situ is difficult. In kidneys with collapsed interstitial spaces distinction of the different interstitial cell types is barely possible; therefore investigation needs good tissue pres- ervation. The various cell types - fibroblasts and cells of the immune system - are narrowly adjacent within the same compartment and may share several structural fea- tures. Unequivocal immunochemical markers, allowing