title: Hemozoin stability and dormant induction of heme oxygenase in hemozoin-fed human monocytes.
abstract: Human monocytes avidly ingest malarial pigment, hemozoin. Phagocytosed hemozoin persists in the monocyte for a long time and modifies important monocyte functions. Stability of phagocytosed hemozoin may depend on modifications of the hemozoin heme moiety or reduced ability to express heme-inducible heme oxygenase. We show here that the spectral characteristics of alkali-solubilized hemozoin were identical to those of authentic heme, although hemozoin was solubilized by alkali much more slowly than authentic heme. Alkali-solubilized hemozoin was a substrate of microsomal rat heme oxygenase and bilirubin reductase, with bilirubin as the main final product. Hemozoin feeding to human monocytes did not induce heme oxygenase, but authentic heme and alkali-solubilized hemozoin supplemented to hemozoin-fed monocytes induced heme oxygenase and were degraded normally. Lysosomes isolated from hemozoin-fed monocytes released only traces of heme while lysosomes from erythrocyte-fed monocytes liberated considerable quantities of heme. Lack of heme release from hemozoin did not depend on proteolysis-resistant, heme-binding proteins, since lysosomal proteases fully degraded hemozoin-associated proteins but did not solubilize hemozoin. In conclusion, our data indicate that lack of induction of HO1 is due to the intrinsic structural characteristics of hemozoin and not to hemozoin-mediated impairment of the mechanism of HO1 induction.
authors.affiliation: Dipartimento di Genetica, Biologia e Biochimica, University of Torino, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Schwarzer
authors.forename: F
authors.initials: F
authors.lastname: De Matteis
authors.forename: G
authors.initials: G
authors.lastname: Giribaldi
authors.forename: D
authors.initials: D
authors.lastname: Ulliers
authors.forename: E
authors.initials: E
authors.lastname: Valente
authors.forename: P
authors.initials: P
authors.lastname: Arese
mesh_terms: D000818:Animals; D004790:Enzyme Induction; D004912:Erythrocytes / Q000469:parasitology; D005978:Glutathione / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D006420:Hemeproteins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008705:Methemalbumin / Q000494:pharmacology; D009000:Monocytes / Q000201:enzymology*; D010587:Phagocytosis; D010963:Plasmodium falciparum / Q000502:physiology*
chemical_list: D006420:Hemeproteins; D008705:Methemalbumin; C020753:hemozoin; D006418:Heme; D006419:Heme Oxygenase (Decyclizing); D005978:Glutathione