Putative innate immunity of antiatherogenic paraoxanase-2 via STAT5 signal transduction in HIV-1 infection of hematopoietic TF-1 cells and in SCID-hu mice.

Paraoxanase-2 (PON2) activity was increased upon HIV-1 infection of the CD34+CD4+ hematopoietic cell line TF-1. Thymocytes derived from the human fetal conjoint thymus/liver hematopoietic organ of SCID-hu mice also exhibited an increase in PON2 activity. Additionally, a remarkable increase of PON2 mRNA expression was also observed in both TF-1 and thymocytes following HIV-1 infection.

HIV-1 determinants of thrombocytopenia at the stage of CD34+ progenitor cell differentiation in vivo lie in the viral envelope gp120 V3 loop region.

HIV-1 V3 loop clones of virus isolates derived from patients suffering from thrombocytopenia were used for infection of the human thymus/liver conjoint hematopoietic organ that developed in the severe combined immunodeficient mouse (SCID-hu Thy/Liv). The V3 loop clones showed a significantly greater degree of inhibition of megakaryopoiesis than myelopoiesis and erythropoiesis of the human CD34+ progenitor cells, in vivo. Inhibition of megakaryopoiesis occurs through reduction in c-Mpl expression and consequent decrease in STAT5 activation.

Rescue of multi-lineage hematopoiesis during HIV-1 infection by human c-mpl gene transfer and reconstitution of CD34+ progenitor cells in vivo.

Cytopenias arising from hematopoietic abnormalities are a severe common complication contributing to early mortality in HIV/AIDS patients. The proto-oncogene c-mpl, identified as the thrombopoietin receptor is involved in multilineage differentiation of CD34+ hematopoietic progenitor cells. We have introduced the c-mpl gene into CD34+ cells via transduction of the lentivirus p156RRLsinPPTmPGK-CMPL-PRE.

Molecular and functional analyses of two new calcium-activated chloride channel family members from mouse eye and intestine.

Two new calcium-activated chloride channel (CLCA) family members, mCLCA5 and mCLCA6, have been cloned from mouse eye and intestine, respectively. mCLCA5 is highly homologous to hCLCA2, and mCLCA6 is highly homologous to hCLCA4. mCLCA5 is widely expressed with strong expression in eye and spleen, whereas mCLCA6 is primarily expressed in intestine and stomach.