[Macromolecular basis of filtration and immune complex pathogenesis in the glomerulus]

Fractional clearance and ultrastructural studies produce results consistent with the idea that the glomerular filtration barrier is a heteroporous membrane. The majority of the pores being small, excluding molecules like serum albumin and larger moieties, while a low number of pores allow the passage of molecules as big as dimeric ferritin, in very restricted quantities. Cationic macromolecules, of a size which should effectively exclude them from the filtration process, readily gain access to all three layers of the GBM. Depending on charge (pI) and size they can in fact exhibit significant affinity for negatively charged structures in both laminae rarae. In addition, polycations can mediate the glomerular deposition of anionic macromolecules, for example DNA-fragments, by diminishing charge repulsion. A prerequisite for the local formation of glomerular immune complexes is that at least one of the reaction partners has an affinity for the GBM. Antigens bound to structures in the laminae rarae are accessible for circulating antibody. Immune complexes formed with cationic antigen in the lamina rara interna are transferred to the subepithelial region with time. Antigen and antibody molecules can penetrate the lamina densa only in dissociated form. The persistence of glomerular immune complexes can be explained by antigen-antibody lattice formation within the network of proteoglycan chains, followed by covalent binding between components of the complex and structures of the GBM.