Alteration of podocytes in a murine model of crescentic glomerulonephritis.
Recent observations suggest a central role of podocytes in crescent formation. In experimental glomerulonephritis podocytes disrupt the parietal epithelial layer and attach on its basement membrane, thus forming bridges between the tuft and Bowman's capsule, and they are a major constituent of crescents. In order to explain these findings we hypothesize that inflammation triggers motility in podocytes. In the present study we asked whether podocytes display alterations which suggest a migratory behavior in glomerulonephritis. Glomerulonephritis was induced in mice by injection of a rabbit serum against the glomerular basement membrane. The kidneys were perfusion-fixed 6 days later and examined by light and electron microscopy as well as by immunohistochemistry. In glomerulonephritis the apical cytoplasm of podocytes displayed numerous actin-containing microprotrusions. Cortactin, a protein involved in the regulation of actin polymerization, was predominantly expressed in foot processes of podocytes in control mice. It was redistributed to the cell body in glomerulonephritis. In untreated mice betal-integrin was restricted to the foot processes. In glomerulonephritis it was additionally found in the cytoplasm and in the apical cell membrane. Recycling of integrins is a crucial event in initiation of cell migration. ICAM-1 and CD44, the ligation of which induces migratory behaviors, were absent from healthy podocytes but expressed by some podocytes in glomerulonephritis. Thus, in glomerulonephritis podocytes display some characteristic features of migrating cells. This might explain their ability to break through the parietal epithelium and to become a constituent of early crescents.
Besse-Eschmann
Valérie
V
Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Le Hir
Michel
M
Endlich
Nicole
N
Endlich
Karlhans
K
D000199:Actins / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D002467:Cell Nucleus / Q000473:pathology; D002478:Cells, Cultured; D051356:Cortactin; D005260:Female; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000473:pathology*; D018960:Hyaluronan Receptors / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D019012:Integrin beta1 / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D016707:Tissue Fixation
D000199:Actins; D051356:Cortactin; C495869:Cttn protein, mouse; D018960:Hyaluronan Receptors; D007074:Immunoglobulin G; D019012:Integrin beta1; D008840:Microfilament Proteins; D018799:Intercellular Adhesion Molecule-1