Interferon Induction by HIV-1-Infected Cells: A Possible Role of Sulfatides or Related Glycolipids

AbstractWe have investigated the mechanism of interferon (IFN) induction in peripheral blood mononuclear cells by HIV-1(IIIB)-infected H9 cells or by recombinant gp120. A monoclonal antibody specific for the galactosylsphingosinyl moiety in galactocerebrosides and sulfatides inhibited IFN induction in a dose-dependent manner. Furthermore, exogenous sulfatides inhibited with an ID50of approximately 1 μM,whereas galactocerebrosides were not inhibitory at 40 times higher concentrations. These studies suggest that sulfate containing galactolipids such as sulfatides on responder cells may be part of the gp120–membrane complex that initiates the induction of IFN. A partial homology of an epitope on the V3 loop of gp120 with a previously suggested binding domain for sulfated glycoconjugates supports this conclusion

Elevated Serum Levels of Osteopontin in HCV-Associated Lymphoproliferative Disorders.

Hepatitis C virus (HCV) infection is associated with chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Recent evidences have also suggested that HCV infection contributes to development of autoimmune disorders and B-cell nonHodgkin's lymphoma (NHL). Mechanisms by which HCV infection promotes B-cell NHL development remain unclear. Increased serum osteopontin (OPN) levels have been associated with several autoimmune diseases as well as a variety of cancers. However, the association between OPN and B-cell NHL or HCV-associated B-cell proliferation has not previously been reported. In the present study, we determined whether serum OPN differences were associated with HCV infection, type II mixed cryglobulinemia (MC) syndrome and B-cell NHL. Serum OPN levels were measured by capture enzyme-linked immunosorbent assay. Our results show that high serum OPN levels are associated with B-cell NHL and HCV infection. Interestingly, highest serum OPN concentrations were found among HCV-infected patients with concomitant type II MC syndrome with and without B-cell NHL. These data indicate that OPN is involved in the lymphomagenesis, especially, in the context of HCV infection and autoimmune diseases

Recombinant interferon alpha-2 modulates hairy cell phenotype "in vitro".

The "in vitro" effect of IFN-alpha on the phenotypic profile of atypical cells from 5 hairy cell leukemia patients was investigated in a 72 hr culture assay. Cytochemical investigations revealed a dramatic decrease in the cytoplasmic content of acid phosphatase and tartrate resistant acid phosphatase in the absence of any apparent morphological modification. Flow cytometry showed that IFN-alpha markedly reduced the density of surface Ig without modifying the original isotype pattern. The expression of the receptor for the Fc fragment of IgG was also reduced. The class II MHC antigen recognized by the monoclonal antibody 12 remained essentially unchanged. Hairy cells were negative for OKT10 and PCA-1 and remained so after IFN-alpha incubation. Present data indicate that IFN-alpha is able to consistently and selectively affect membrane and cytoplasmic features of hairy cells in a short term period. The possibility is envisaged that these changes may be related to the therapeutic efficacy of IFN-alpha