Heme on Pulmonary Malaria: Friend or Foe?

Abstract

Malaria is a hemolytic disease that, in severe cases, can compromise multiple organs. Pulmonary distress is a common symptom observed in severe malaria caused by Plasmodium vivax or Plasmodium falciparum. However, biological components involved in the development of lung malaria are poorly studied. In experimental models of pulmonary malaria, it was observed that parasitized red blood cell-congested pulmonary capillaries are related to intra-alveolar hemorrhages and inflammatory cell infiltration. Thus, it is very likely that hemolysis participates in malaria-induced acute lung injury. During malaria, heme assumes different biochemical structures such as hemin and hemozoin (biocrystallized structure of heme inside Plasmodium sp.). Each heme-derived structure triggers a different biological effect: on the one hand, hemozoin found in lung tissue is responsible for the infiltration of inflammatory cells and consequent tissue injury; on the other hand, heme stimulates heme oxygenase-1 (HO-1) expression and CO production, which protect mice from severe malaria. In this review, we discuss the biological mechanism involved in the dual role of heme response in experimental malaria-induced acute lung injury.

Hematin- and Hemin-Induced Spherization and Hemolysis of Human Erythrocytes Are Independent of Extracellular Calcium Concentration

“…Hematin (ferric (Fe 3+ ) PP IX liganded with OH − ) is formed predominantly during malaria RBC invasion as a by-product of the parasite’s digestion of host cell hemoglobin (Hb), while hemin (Fe 3+ PP IX liganded with Cl − ) is constantly produced in the human body during the reactions of Hb autooxidation either spontaneous or disease-triggered ( Supplementary Figure S1 ) [ 10 ]. Both compounds were shown to induce complications such as vascular occlusion, pulmonary damage, secondary brain injury, and kidney or liver damage [ 11 , 12 , 13 , 14 ].…”

Inhibition of Heme Oxygenase-1 by Zinc Protoporphyrin IX Improves Adverse Pregnancy Outcomes in Malaria During Early Gestation

“…Malaria is a hemolytic disease caused by protozoan parasites of the genus Plasmodium , in which heme released during the rupture of red blood cells leads to oxidative damage due to the production of reactive oxygen species that induce inflammation and tissue damage ( 3 , 4 ). Because heme is also toxic to parasites, they turn heme into a non-toxic product, the malarial pigment known as hemozoin ( 5 ).…”