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The mesangium and glomerulonephritis

Das Mesangium und Glomerulonephritis

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Summary

The mesangium of the glomerular capillary ultrafilter is a specialized pericapillary tissue. In adult mammals its location is limited to the axial portions of the loop, but it extends peripherally to encircle the capillary in the fetal state and in certain glomerular diseases. It contains predominantly intrinsic mesangial cells, which resemble contractile endocytic capillary pericytes, and which are embedded in the extracellular matrix. In addition, the mesangial space normally harbors few resident Ia-antigen bearing, immune-competent cells and rare transient monocyte-macrophages. Due to its unique location between the fenestrated endothelial lining of the capillary lumen and the glomerular basement membrane, constituting the filtration barrier, the mesangium is prone to deposition of potentially noxious plasma constituents and filtration residues, such as phlogogenic foreign proteins and immune complexes. The determinants of the mesangial entry, uptake and removal of such materials are presently incompletely understood but they are thought to include the amount and nature of the deposit, local hemodynamic factors and the ability of the mesangium to degrade or to eliminate the deposited agent. Histopathologic studies of various human and experimental glomerular diseases reveal that increased mesangial cell proliferation and matrix widening may occur either in direct response to deposits or induced by mediators released from inflammatory cells, such as monocyte-macrophages. While the functional damage to the glomerular filter is usually mild when the reaction is limited to the mesangial space, it is more pronounced when the mesangial abnormalities are secondary to subendothelial deposits of the peripheral capillary wall. Recent experimental data indicate that a mesangial inability in removing deposited material may develop in certain chronic glomerular disorders characterized by marked proteinuria, glomerular hypertension and hyperfiltration or accumulation of matrix material. Such states of mesangial dysfunction may play a critical role in the pathogenesis of progressive glomerular sclerosis. It is concluded that better understanding of the pathophysiology of the mesangium would be valuable for designing more effective diagnostic and therapeutic approaches to patients with glomerular disease.

Zusammenfassung

Im glomerulären Ultrafilter findet sich das Mesangium als ein spezialisiertes perikapilläres Gewebe. Bei ausgewachsenen Säugern ist es auf die axialen Abschnitte der Kapillarschlingen begrenzt, während es im Foetalstadium und bei manchen glomerulären Erkrankungen die Kapillare völlig umgibt. Die anzahlmäßig weit überwiegenden eigentlichen Mesangiumzellen, die in eine extrazelluläre Matrix eingebettet sind, besitzen die Fähigkeit zur Kontraktion und Endozytose und ähneln somit Kapillarperizyten. Zusätzlich sind im Mesangialraum normalerweise einige Ia-Antigen-positive, immunologisch kompetente Zellen angesiedelt und selten finden sich wandernde Monozyten-Makrophagen. Das Mesangium liegt zwischen dem gefensterten Endothel der Kapillare und der glomerulären Basalmembran, der eigentlichen Filtrationsbarriere. Aŭfgrund dieser ganz besonderen Lage ist das Mesangium prädestiniert für die Aufnahme von möglicherweise schädlichen Plasmabestandteilen und Filtrationsrückständen, wie z.B. entzündungsauslösenden Fremdeiweißen und Immunkomplexen. Die Faktoren, die mesangiale Aufnahme und Eliminierung von derartigen Substanzen bestimmen, sind derzeit nicht genau bekannt. Es wird angenommen, daß hierbei neben Menge und Eigenschaften der Ablagerungen auch hämodynamische Faktoren eine Rolle spielen, sowie die Fähigkeit des Mesangium, die abgelagerten Substanzen abzubauen oder zu entfernen. Histopathologische Untersuchungen verschiedener humaner und tierexperimenteller glomerulärer Erkrankungen zeigen, daß die mesangialen Veränderungen gewöhnlich aus Zellproliferation und Zunahme der Matrix bestehen. Sie stellen entweder eine direkte Reaktion auf die abgelagerte Substanz dar, oder sie werden durch Mediatoren induziert, die von Entzündungszellen, wie z.B. Monozyten-Makrophagen, freigesetzt worden sind. Ist eine solche Reaktion auf den Mesangialraum begrenzt, wird die glomeruläre Funktion gewöhnlich nur geringfügig beeinträchtigt. Hingegen findet sich eine stärker ausgeprägte Funktionseinbuße, wenn die mesangialen Schäden durch subendothelial abgelagertes Material in der peripheren Kapillarschlinge ausgelöst worden sind. Neuere experimentelle Ergebnisse weisen daraufhin, daß sich eine mesangiale Insuffizienz hinsichtlich der Elimination von Ablagerungen bei manchen chronischen glomerulären Störungen entwickeln kann, zumal wenn diese durch starke Proteinurie, glomeruläre Blutdruckerhöhung und Hyperfiltration oder Matrixzunahme gekennzeichnet sind. Derartige Zustände von „mesangialer Dysfunktion“ könnten eine entscheidende Rolle in der Pathogenese von fortschreitender glomerulärer Sklerose spielen. Eine Verbesserung unserer Kenntnisse über die Pathophysiologie des Mesangium wäre von Bedeutung für die Entwicklung wirksamer diagnostischer und therapeutischer Maßnahmen bei Patienten mit glomerulären Krankheiten.

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  1. Departments of Medicine and Pathology, Veterans Administration Medical Center and Yale University School of Medicine, West Haven, CT, USA

    R. B. Sterzel MD, D. H. Lovett, H. D. Stein & M. Kashgarian

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  3. H. D. Stein
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Supported by grants from the Veterans Administration, Washington, DC

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Sterzel, R.B., Lovett, D.H., Stein, H.D. et al. The mesangium and glomerulonephritis. Klin Wochenschr 60, 1077–1094 (1982). https://doi.org/10.1007/BF01715838

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