Pharmacologic effects of the red blood cell substitutes cross-linked and non-cross-linked hemoglobins on hematopoiesis in rabbits.

The red blood cell substitutes beta-beta cross-linked (DECA-Hb, XLBV-Hb) and non-cross-linked (HbA) hemoglobins (Hbs), were transfused into rabbits and their effects on hematopoiesis examined. All rabbits receiving DECA-Hb or XLBV-Hb tolerated the Hbs well, whereas 50% of the animals transfused with similar doses of non-cross-linked HbA died. Analysis of peripheral blood and bone marrow BFU-E and CFU-GM production revealed that there was no significant variation in the generation of BFU-E and CFU-GM numbers for each cross-linked Hb transfusion group, but there were significant reductions in the HbA group.

Heme oxygenase induction with attenuation of experimentally induced corneal inflammation.

Heme oxygenase (HO), by catabolizing heme to bile pigments, down-regulates cellular levels of heme and hemeproteins; certain of the latter, i.e. cytochrome P450s, generate pro-inflammatory products from endogenous substrates.

Zinc porphyrins: potent inhibitors of hematopoieses in animal and human bone marrow.

The effects of selected heme analogues on heme oxygenase activity in tissues and on human and rabbit bone marrow hematopoietic colony growth were examined. Zinc protoporphyrin (ZnPP) and zinc mesoporphyrin (ZnMP), at concentrations ranging between 1 and 20 microM, produced significant inhibition of human and rabbit bone marrow erythroid (CFU-E, BFU-E) and myeloid (CFU-GM) colony growth. The growth inhibition produced by ZnPP or ZnMP was not overcome with exposure of cultures to elevated levels of the growth factors erythropoietin and granulocyte-macrophage colony stimulating factor.

Inhibition of human immunodeficiency virus-1 reverse transcriptase by heme and synthetic heme analogs.

Heme and a series of synthetic heme analogs were tested for inhibition of human immunodeficiency virus-1 (HIV-1) reverse transcriptase (RT) activity. Heme and the protoporphyrin complexes of cadmium, magnesium, and tin significantly inhibited HIV-1 RT, whereas other metalloporphyrins had a lesser or no effect on the enzyme. The mechanism of inhibition was examined with respect to heme and tin protoporphyrin (SnPP), as both compounds have been utilized clinically as treatment for noninfectious disorders.

Transfer of human adenine deaminase gene into murine hematopoietic stem cells: sequential study of spleen colony-forming units from bone marrow of living mice and the requirement of the microenvironment.

Irradiated female mice were reconstituted with male hematopoietic stem cells (HSCs) retrovirally marked with human adenine deaminase (hADA) complimentary DNA. HSCs were incubated with interleukin-6 and stem cell factor before coculture with GP+E86-producing cells. Bone marrow HSCs were infused intravenously to irradiated mice and spleen colony-forming units (CFU-S) were evaluated for hADA marked clones by Southern blot analysis.