Hemozoin stability and dormant induction of heme oxygenase in hemozoin-fedhuman monocytes

Human monocytes avidly ingest malarial pigment, hemozoin. Phagocytosed hemo zoin persists in the monocyte for a long time and modifies important monocy te functions. Stability of phagocytosed hemozoin may depend on modification s of the hemozoin heme moiety or reduced ability to express heme-inducible heme oxygenase. We show here that the spectral characteristics of alkali-so lubilized hemozoin were identical to those of authentic heme, although hemo zoin 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 fee ding to human monocytes did not induce heme oxygenase, but authentic heme a nd alkali-solubilized hemozoin supplemented to hemozoin-fed monocytes induc ed heme oxygenase and were degraded normally. Lysosomes isolated from hemoz oin-fed monocytes released only traces of heme while lysosomes from erythro cyte-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 pro teins but did not solubilize hemozoin. In conclusion, our data indicate tha t lack of induction of HO1 is due to the intrinsic structural characteristi cs of hemozoin and not to hemozoin-mediated impairment of the mechanism of HO1 induction. (C) 1999 Elsevier Science B.V. All rights reserved.