Trypsin treatment of adherent human monocytes greatly reduced or eliminated the ability of these cells to support dengue virus replication. However, addition of dilute (nonneutralizing) antibody to the inoculum and the culture medium resulted in viral yields similar to those from monocytes not treated with trypsin. These results suggested that viral entry was facilitated by phagocytosis of immune complexes via Fc receptors on the monocytes. This concept was tested by (i) pretreating monocytes with aggregated gamma globulin, which resulted in a 40-fold reduction of viral yields after infection with dilute antibody-virus complexes and (ii) forming an immune complex with virus, antivirus F(ab')2 fragments, and rabbit anti-human Fab. Whereas F(ab')2 fragments alone would not enhance virus replication in trypsin-treated monocytes, the immune complex containing a rabbit Fc piece did increase the yield of dengue virus. These results suggest that dengue virus can infect a cultured monocyte in two ways: (i) through a viral receptor that is trypsin sensitive or (ii) through an Fc receptor that is not trypsin sensitive.
Peripheral blood monocytes from patients with active sarcoidosis have increased ability to bind IgG-antibody-coated and C3-coated erythrocytes. Binding of monocytes from sarcoid patients is inhibited less than for normals with IgG1 and IgG3 in the fluid phase. Following phagocytosis of latex particles, monocytes from sarcoides patients retain the capacity to bind IgG-coated erythrocytes, whereas monocytes from normal individuals show disappearance of IgG receptors followed by recovery during a 6-8 hr period. Preliminary studies (8 patients) of monocytes from patients with Crohn's disease show some increase in binding of IgG-coated erythrocytes as compared with normals; this increase, however, is less than for sarcoidosis patients. Preliminary experiments with multistranded polynucleotides (poly I:C:U) show increased activity for normal monocytes and no detectable effect on IgG receptor activity for sarcoid monocytes. Thus peripheral blood monocytes of patients with sarcoidosis have increased IgG and C3 receptors sites, suggesting activation of monocytes in this disease and perhaps in other granulomatous disorders.
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