Antibodies that enhance human immunodeficiency virus (HIV) infectivity have been found in the blood of infected individuals and in infected or immunized animals. These findings raise serious concern for the development of a safe vaccine against acquired immunodeficiency syndrome. To address the in vivo relevance and mechanism of this phenomenon, antibody-dependent enhancement of HIV infectivity in peripheral blood macrophages, lymphocytes, and human fibroblastoid cells was studied. Neither Leu3a, a monoclonal antibody directed against the CD4 receptor, nor soluble recombinant CD4 even at high concentrations prevented this enhancement. The addition of monoclonal antibody to the Fc receptor III (anti-FcRIII), but not of antibodies that react with FcRI or FcRII, inhibited HIV type 1 and HIV type 2 enhancement in peripheral blood macrophages. Although enhancement of HIV infection in CD4+ lymphocytes could not be blocked by anti-FcRIII, it was inhibited by the addition of human immunoglobulin G aggregates. The results indicate that the FcRIII receptor on human macrophages and possibly another Fc receptor on human CD4+ lymphocytes mediate antibody-dependent enhancement of HIV infectivity and that this phenomenon proceeds through a mechanism independent of the CD4 protein.
We have demonstrated that one Fc receptor for IgG (FcR) (CD16) on cultured human monocytes appears to be a developmentally regulated membrane protein. This receptor appears to contain less carbohydrate (if any) than does its counterpart on human neutrophils. Expression of CD16 on cultured monocytes increases with respect to both percentage of positive cells and numbers of sites per cell with length of time in culture. This was in contrast to expression of other types of FcRs that either decreased (CDw32) or did not change (FcRp72). Unlike an FcR that binds monomeric IgG (FcRp72), expression of CD16 on monocytes from most normal individuals was not influenced by IFN-gamma. After 14 d in culture, CD16 appeared to be the predominant FcR on cultured monocytes, and was capable of mediating both ligand attachment and phagocytosis. These findings support the hypothesis that CD16 plays an important role in mediating immunophagocytosis.
1. The range of free cholesterol in the blood of rabbits, as determined by the Windaus method, varies from 35 to 125 mg. with a mean of 71 mg. per 100 cc. of blood.
2. The small amount of cholesterol contained in the high protein diet used by us in earlier work and causing atherosclerosis does not affect the blood cholesterol nor does it cause arterial disease.
3. In order to produce atherosclerosis it is necessary to feed at least ten times that amount of cholesterol.
4. In rabbits receiving such amounts both hypercholesterolemia and atherosclerosis occur, but it is not possible to establish any close parallelism between the two. High blood readings are found in rabbits with normal aortæ and atherosclerotic rabbits in this series sometimes have shown a normal blood cholesterol.
5. With still greater doses of cholesterol one finally reaches an amount which regularly produces hypercholesterolemia and atherosclerosis within a few weeks.
6. A new series of rabbits fed the high protein diet shows that those rabbits which become atherosclerotic also develop hypercholesterolemia. We attribute this elevation of the blood cholesterol to a metabolic disturbance directly referable to the excess of protein in the diet and not to its cholesterol content.
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