Mobilization of cells from the bone marrow to the blood using recombinant G-CSF is the most often used therapy for the treatment of neutropenia or harvesting hematopoietic stem cells (HSC) for transplantation. We discovered that cobalt protoporphyrin IX (CoPP) increases endogenous G-CSF expression and induces mobilization of cells from the bone marrow to the blood in mice. However the question remains if CoPP could be used as a drug for mobilization purposes and if it could work

better than recombinant G-CSF. The long-term goal of our studies is to develop the new therapeutic strategy for mobilization of cells to the blood. Consequently, the overall objective of this project is characterize the phenotype and clinically relevant functional properties of the cells mobilized by CoPP and compare them to the cells mobilized by recombinant G-CSF. We hypothesize that CoPP induces multiple mobilizing factors, leading to greater mobilization of HSC and of mature granulocytes compared to G-CSF alone. Under Aim 1 we will optimize dosage and length of treatment with CoPP enabling effective mobilization of granulocytes and HSCs by injecting mice with various doses of CoPP or recombinant G-CSF and evaluating granulocyte and HSC numbers in blood at various time points after injection. Under Aim 2 we will incubate granulocytes isolated from mice treated with CoPP or G-CSF with selected pathogens and assess the percentage of killing by plating on agar plates in order to compare the maturity of CoPP- and G-CSF-mobilized granulocytes. In Aim 3 we will compare the engraftment efficiency of CoPP and G-CSF-mobilized HSCs. Completion of this project will provide critical preclinical validation of CoPP as a potential agent for mobilization of cells from the bone marrow in the treatment of blood disorders, such as neutropenia or leukemia.