The effect of heparin on the handling of immune complexes in the renal glomerulus.

This thesis describes work performed to establish the mechanism by which heparin is found to remove established immune complex deposits from nephritic glomeruli. Is also looks at the effect of heparin on the handling of immune complexes by glomerular mesangial cells in culture. In vivo experiments, along with in vitro kidney perfusions, established that the effect of heparin was independent of its size and its anticoagulant properties, whilst the effect was dependent on its charge. In cell culture it was established that heparin was able to inhibit immune complex binding to mesangial cells. Heparin was also found to be capable of removing bound immune complexes. Its effect on cells in culture was found to be both charge and size dependent, with low molecular weight compounds being incapable of either inhibiting immune complex binding or removal of bound immune complexes. The conclusions drawn from this are two fold. In the cell culture system heparin's charge and heparin's size are both important for immune complex removal. In the whole animal and in the isolated perfused kidney heparin's charge is important for immune complex removal, whereas its size was not found to be important. The differences between the cell culture and the whole animal system have established that although cell culture may be a useful method for the primary evaluation of drug effects, trial in the whole animal remains the best way to fully establish their effect on immune complex removal.