Specific ligation of the HIV-1 viral envelope protein gp120 on human CD34+ bone marrow-derived progenitors.

The precise mechanisms of hematologic abnormalities observed during HIV infection remain unknown. In vitro experiments performed by various authors concerning the HIV toxicity on bone marrow-derived precursors did not allow them to determine whether this toxicity could be mediated through direct or non-direct effects, since it is today unclear if gp120 possesses a direct hematotoxic effect on human bone marrow progenies. The aim of our study was to determine whether labelled gp120 could specifically bind to the membrane of purified human normal CD34+ cells and to investigate the in vitro effect of the gp120 on their growth. To answer these questions, human CD34+ cells were purified from normal bone marrow samples, then labelled with monoclonal antibodies directed either against CD4 antigen or CD34 antigen and/or with FITC labelled gp120 and analyzed by FACS. Our results demonstrate the presence of about 5% of CD4+CD34+ cells and of nearly 12% of CD34+gp120+ precursors. Together with our results concerning the in vitro inhibitory effect of gp120 on the growth of the same purified CD34+ precursors, our data demonstrated the direct hematotoxic activity of HIV-derived gp120 and the possible HIV infection of hematopoietic progenitors through the interaction of gp 120 with CD34+ cell surface.

[Demonstration of a protector effect of interleukin-1 against hematologic toxicity of azidothymidine (AZT)]. / Mise en évidence d'un effet protecteur de l'Interleukine-1 vis-à-vis de la toxicité hématologique de l'azidothymidine (AZT).

3'-azido-3'-deoxythymidine (Azidothymidine or AZT) has attained wide critical utility in the treatment of acquired immunodeficiency syndrome (AIDS). Unfortunately, treatment with AZT is associated with the development of severe hematopoietic toxicity. The AZT sensitivity of marrow progenitors was different with an IC 50 of 10(-8) M and 10(-6) M for respectively BFU-E and CFU-GM/GEMM. Data reported here show that recombinant human interleukin-1 alpha (IL-1 alpha), a pleiotropic cytokine, was demonstrated to be efficient to protect normal human as well as murine hematopoietic progenitors (CFU-GM, CFU-GEMM and BFU-E) from the toxic effect of AZT. The maximal effect was observed with 30 U/ml (Human cells) or 100 U/ml (murine cells) IL-1 alpha for BFU-E and CFU-GM/GEMM, with a marked effect at 1 U/ml. The results demonstrate that marrow progenitors respond differently to AZT and point out the potential efficacy of IL-1 alpha to enhance the proliferation of hematopoietic stem cells treated with growth factors (IL-3, erythropoietin) and to minimize the hematopoietic toxicity associated with AZT treatment.