Marco Giovannini

Human immunodeficiency virus type 1 envelope glycoprotein gp120-mediated killing of human haematopoietic progenitors (CD34+ cells).

The effects of human immunodeficiency virus type 1 (HIV-1) and recombinant envelope glycoprotein gp120 on the in vitro growth of enriched human haematopoietic progenitors (CD34+ cells) have been investigated. A 2 h exposure to HIV-1 resulted in a progressive and significant reduction of viable CD34+ cell number in liquid cultures and of granulocyte-macrophage, erythroid and megakaryocytic progenitors in semisolid cultures. In virus-treated CD34+ cells, no signs of active virus replication were observed and the possibility of latent infection was excluded by quantitative polymerase chain reaction. Recombinant HIV-1 envelope glycoprotein gp120 added to CD34+ cell cultures displayed a dose-dependent inhibitory activity on CD34+ cell viability. Neutralizing antibody against gp120 was able to block completely the inhibitory activity on CD34+ cells of either HIV-1 or recombinant gp120. These results demonstrate that HIV-1 envelope glycoprotein gp120 has a direct cytotoxic effect on CD34+ cells.

The inhibitory effect of serum from hairy‐cell leukaemia patients on normal progenitor cells may disappear following prolonged treatment with α‐interferon

Summary The possibility that serum from hairy‐cell leukaemia (HCL) patients at diagnosis may show an inhibitory effect on the in vitro colony growth of normal haemopoietic progenitor cells has been suggested. Several studies have documented the efficacy of α‐Interferon (α‐IFN) in inducing a complete restoration of peripheral blood values and, in some cases, a complete clinical remission. In this study we have evaluated the regulatory effect of serum, collected before and after 3 and 12 months of a‐IFN tretment, from 10 patients with untreated HCL, on the in vitro growth of normal bone marrow CFU‐GM, BFU‐E and CFU‐MK. The effect of conditioned media, prepared from enriched hairy cells (HC) cultured in synthetic medium, on the growth of normal haemopoietic progenitors was also investigated. The results obtained confirm that sera from untreated HCL patients display a variable degree of inhibitory activity in the progenitor cell compartments analysed. Disappearance of the inhibitory activity, particularly evident for the erythroid compartment, was found only in patients who displayed a disappearance of circulating HC and a good haematological response after prolonged (12 months) treatment with a‐IFN. The possibility that the serum of patients with HCL may contain a haemopoietic inhibitory factor, released by the neoplastic HC population, is suggested.

Effect of human immunodeficiency virus type 1 on CD34+ cells.

The effect of HIV-1 on the in vitro growth of enriched hematopoietic stem cells (CD34+ cells) obtained from normal peripheral blood samples was studied. In comparison to untreated controls, the number of viable CD34+ cells progressively and significantly decreased in liquid cultures containing interleukin-3 (IL-3, 100 U/ml) after inoculation with HIV-1. In inoculated samples there was a significant reduction of all the hematopoietic progenitors (CFU-GM, BFU-E, CFU-Meg) starting from the second day of culture, CFU-GM being the most affected. In spite of these findings, no evidence of viral replication was observed: the total amount of p24 in HIV-1-inoculated CD34+ cell cultures showed a plateau, slightly declining towards the end of the experimental observation period. Moreover, erythroid and granulomacrophage colonies harvested from inoculated CD34+ cell cultures were unable to infect susceptible cells.

Giant cell tumor of bone: a model for the in vitro human osteoclast characterization.

The in vitro growth pattern of cells obtained from bioptic material of ten patients with giant cell tumor of bone (GCT) was investigated. Cytochemical reactions and monoclonal antibodies raised against macrophage markers were tested on the two histologically identifiable GCT cell populations. Only monoclonal antibody EBM/11 stained both mononuclear and giant cells. EBM/11 positivity and resistance of acid phosphatase to high doses of tartrate strongly suggest that both mononuclear and giant cells belong to the same lineage.