Nephrology & Therapeutics

Biography

Biography: Bernd H Zinselmeyer

Abstract

The combination of murine transplantation models, fluorescent reporter mice and intravital 2-photon microscopy enables an unprecedented view on the initiation of transplant rejection. In murine allogeneic models of lung transplantation we could observe the innate arm of the immune-system of the host. Minutes after transplantation neutrophils of the host regularly aggregated in dynamic clusters that formed and dispersed in the allogeneic transplant. These clusters were associated with CD115+ F4/80+ Ly6C+ host cells that had immediately entered the lung. Observing the adaptive arm of the immune system we could explain why allogenic lungs can be rejected in the absence of secondary lymphoid organs. Two-photon microscopy revealed that recipient T-cells are activated predominantly around lung-resident, donor-derived CD11c+ cells. These findings might be singular for the lung; however they demonstrate the value of intravital multiphoton imaging in the study of transplant rejection. Very recently we started using two-photon microscopy to study the three-dimensional structure of mouse podocytes in high temporal resolution in the present absence of inflammation. We found that healthy podocytes remained non-motile and maintained a canopy-shaped structure over time. On expression of constitutively active Rac1 or after induction of nephrotoxic nephritis podocytes changed shape by retracting processes and clearly exhibited domains of increased membrane activity. Furthermore, drastic activation of Rac1 also led to podocyte detachment from the glomerular basement membrane, and we observed detached podocytes crawling on the surface of the tubular epithelium and occasionally, in contact with peritubular capillaries. These findings potentially explaining the extinction of foot-process in a wide range of severe kidney-disease.