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(American Journal of Pathology. 2002;160:861-867.)
© 2002 American Society for Investigative Pathology

Regular Articles

The {alpha}8 Integrin Chain Affords Mechanical Stability to the Glomerular Capillary Tuft in Hypertensive Glomerular Disease

Andrea Hartner*, Nada Cordasic*, Bernd Klanke*, Ulrich Müller{dagger}, R. Bernd Sterzel* and Karl F. Hilgers*

From the Medizinische Klinik IV,*
Universität Erlangen-Nürnberg, Erlangen, Germany; and the Friedrich-Miescher-Institut,{dagger}
Basel, Switzerland

In the kidney, the {alpha}8 integrin chain is expressed in glomerular mesangial cells. The {alpha}8 integrin plays a role in early nephrogenesis but its functional role in the adult kidney is unknown. We tested the hypothesis that {alpha}8 integrin-mediated cell-matrix interactions are important to maintain the integrity of the glomerulus in arterial hypertension. Desoxycorticosterone (DOCA)-salt hypertension was induced in mice homozygous for a deletion of the {alpha}8 integrin chain and wild-type mice. Blood pressure, albumin excretion, total renal mass, and glomerular filtration in DOCA-treated {alpha}8-deficient mice were comparable to DOCA-treated wild types. DOCA-treated wild types showed increased glomerular immunostaining for {alpha}8 integrin compared to salt-loaded and untreated controls, whereas the glomeruli of {alpha}8-deficient mice always stained negative. Morphometric studies revealed similar degrees of glomerulosclerosis in DOCA-treated {alpha}8-deficient and DOCA-treated wild-type mice. However, DOCA-treated {alpha}8-deficient mice had a higher score of capillary widening (mesangiolysis) than DOCA-treated wild-type mice, which was confirmed in two additional wild-type strains. Moreover, in DOCA-treated {alpha}8-deficient mice, glomerular fibrin deposits were more frequent than in DOCA-treated wild types. The results show that lack of {alpha}8 is associated with increased susceptibility to glomerular capillary destruction in DOCA salt hypertension, whereas it does not seem to play a major role in the development of fibrosis or glomerulosclerosis. Our findings indicate that mesangial {alpha}8 integrin contributes to maintain the integrity of the glomerular capillary tuft during mechanical stress, eg, in hypertension.




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