Elevated levels of heme oxygenase-1 activity and mRNA in peripheral blood adherent cells of acquired immunodeficiency syndrome patients

Abstract

Patients with the acquired immunodeficiency syndrome (AIDS) commonly develop hematological abnormalities, including anemia, leukopenia, and thrombocytopenia. Heme synthesis and heme degradation are critical to the maintenance of cellular heme homeostasis and to hematopoietic differentiation. We examined heme oxygenase activity and expression of the heme oxygenase gene in adherent cells (monocytes-macrophages) obtained from the peripheral blood of AIDS patients and normal controls. Heme oxygenase activity in normal control cells was 43 +/- 16 pmol bilirubin formed/4 x 10(5) cells/hr as compared to 133 +/- 30 pmol bilirubin formed/4 x 10(5) cells/hr in the AIDS patients. Via blot hybridization analysis with human heme oxygenase cDNA, heme oxygenase mRNA levels in cells of the normal and the AIDS patients were compared. Total RNA from normal cells displayed only weak hybridization with the cDNA probe. In contrast, cells from peripheral blood of the AIDS patients displayed marked increases over normal levels in heme oxygenase mRNA. Heme oxygenase activity could be substantially suppressed by the competitive inhibitor of the enzyme, Sn-mesoporphyrin. Elevated heme oxygenase activity in cells of AIDS patients could produce a decrease in cellular heme needed for transductional signalling for the growth factor network, which regulates the hematopoietic microenvironment, and for other metabolic purposes. Suppression of heme catabolism by inhibitors of this enzyme may thus be useful in potentiating erythropoietic responses in this disorder.