Severe malaria caused by the parasite Plasmodium falciparum is a potentially fatal disease, in part due to the failure of host organs brought about by the accumulation of parasitized red blood cells in the microvasculature. A critical first line of defense that the immune system employs against malaria is the phagocytosis of infected red blood cells by macrophages, either circulating in the blood or resident in the spleen, liver and lungs. However, in order to exploit the macrophage's ability to clear parasites it is first necessary to understand exactly how phagocytic cells damage intraerythrocytic malaria parasites and why they are not always successful in eradicating malarial infection. One major obstacle to understanding how phagocytosis might occur in the microvasculature has been the lack of a tool that closely mimics the in vivo environment of capillaries under controlled laboratory conditions. The goal of this proposal is to establish the feasibility of using a microfluidic system to study for the first time the interaction of infected red blood cells with phagocytic cells under flow conditions in the presence of host ligands. Such a tool would lead to an increased understanding of phagocytosis of malaria-infected erythrocytes in packed capillaries. ? ? ?
