Malaria Pigment

Hemozoin is a stable insoluble crystalline dimer of ferriprotoporphyrin IX formed from indigestible ferric heme after hemoglobin digestion in the parasite food vacuole. After schizogony it is avidly phagocytosed in its native form (which also contains saturated and unsaturated lipids and host fibrinogen) by circulating and resident white cells (monocytes, macrophages, granulocytes) and to a minor extent by endothelial cells. After phagocytosis it exerts a number of inhibitory and activatory effects. It inhibits MHC II and ICAM-1 upregulation, monocyte differentiation to dendritic cells, monocyte motility, ability to repeat phagocytosis; it kills ingested bacteria, fungi, and tumor cells; it enhances the short-term oxidative burst; it generates bioactive lipoperoxidation derivatives (HETEs, HODEs, HNE) that may diffuse to neighboring cells, for example, inhibiting erythropoiesis in the bone marrow. HZ ingestion enhances the formation of a number of proinflammatory cytokines and chemokines responsible for malaria symptoms such as cyclical fevers. In vivo, a correlation has been found between the number of circulating HZ-laden WBC and malaria severity.