Blood Mononuclear Phagocytes Research Articles

Enhancement of dengue virus infection in monocytes by flavivirus antisera.

Enhanced dengue 2 virus (D2V) infection in suspension cultures of human peripheral blood mononuclear phagocytes (PBL) produced by subneutralizing concentrations of dengue antisera has been described previously. In this study, the enhancement phenomenon was found to be a general property of representative flavivirus antisera. All except one of 24 antisera, which had been raised by 1-3 injections of flaviviruses in rabbits, enhanced the growth of dengue 2 virus in human PBL. Flavivirus antisera showing the greatest level of cross-reactivity against a battery of 42 flavivirus antigens in the hemagglutination-inhibition test were most potent in enhancing dengue replication in PBL cultures. Cross-neutralizing reactivity did not relate to enhanced D2V infection. However nearly one-half of studied flavivirus antisera neutralized D2V at dilutions of 1:10 or 1:20. Heterotypic D2V neutralizing antibody could serve as a "brake" on infection enhancement in vivo. Observations should be made in the field to look for possible enhancement of dengue infection in heterotypic flavivirus immunes.

The effect of radiotherapy on blood mononuclear cell numbers and phagocyte migration

The effect of localised radiotherapy on whole blood mononuclear cell numbers are on phagocyte migration has been studied in order to relate the effects of treatment to site and volume of radiation. Thirty nine patients who were receiving radiotherapy to five different sites were studied sequentially before, during, and after treatment. Lymphopenia developed with the onset of treatment in the four groups treated with radiotherapy to a large volume. The fall in lymphocyte count affected both T cells and non-T cells, was exponential throughout the period of irradiation, and the rate was independent of site of treatment. Monocyte numbers and phagocyte migration was unaffected. T cells were slightly more radiosensitive than non-T cells and recovery of T cell numbers was usually slow. No effect was seen when superficial radiotherapy was given to a small volume of skin.

The Milk Mononuclear Phagocyte

A large number of mononuclear phagocytes are present in human colostrum and milk and are transferred from mother to baby. Although one can only speculate on their role in vivo, there is a modest amount of information about their characteristics in vitro which will be reviewed in this paper. About 80% of the one to two million leukocytes in colostrum and early human milk are mononuclear phagocytes1,2 as determined by esterase staining,3 latex ingestion, and glass adherence. While See Table in the PDF Document their concentration diminishes with longer lactation, the number of macrophages secreted daily is large (Table 1). The milk mononuclear phagocyte spreads avidly onto glass surfaces extending long filamentous processes into the environment (Fig 1). Trypan blue is rapidly taken up into the lysozomes of living cells (Fig 2) as is acridine orange. These cells are lipid laden (Fig 3) and on ultrastructural analysis one sees that the lipid inclusions are not always membrane bound (Fig 4). Mitochondria, an indication of oxidative metabolism, and rough and smooth endoplasmic reticulum, suggesting active protein synthesis, are plentiful. Comparisons between milk and blood mononuclear phagocytes are listed in Table 2. Lysozyme is one of the proteins synthesized and secreted by the milk mononuclear phagocyte. By competitive binding, radioimmunoassay milk macrophages can be shown to release 100 ± 8 ng lysozyme/ 5 x 105 cells into the supernatant; the level is reduced to 20 ± 4 ng when these cells are cultured in the presence of 10 µg/ml of cyclohexamide, an inhibitor of protein synthesis. Moreover, it appears that these cells make C3 and C4.

728 THE MILK MONONUCLEAR PHAGOCYTE IS A MACROPHAGE

Mononuclear phagocytic cells (MM) account for 86±2 (±1 SD) of the 1.8±.2×106/cc milk leukocytes in the first week of lactation. MM were isolated by differential centrifugation and glass adherence and their state of differentiation studied with histochemical immunologic, functional and metabolic assays. 31±9% of glass adherent latex ingesting cells stained for peroxidase activity compared to 100% of similarly selected blood mononuclear phagocytes (BM). 83±9% MM and 97±2 BM formed rosettes with SRBC coated with IgM anti-SRBC and the first four complement components (C3bSRBC). 96±3% MM and 97±2% BM formed rosettes with IgGSRBC. Titration of the IgGSRBC to BM or MM ratio required for cosetting revealed that MM had >4 fold avidity for IgGSRBC than BM. MM spread and elongate on glass more rapidly than BM. This phenomenon, the low peroxidase activity, and high avidity for IgGSRBC of MM all suggest that the MM is a macrophage (MØ). IgGSRBC phagocytosis occurred in 85±4% MM and 90±5% BM under similar conditions but C3bSRBC phagocytosis occurred in neither MMnor BM suggesting that the MM is not an activated MØ. MM and BM IgGSRBC phagocytosis were completely inhibited by NaF. BM pretreated with cell free human milk (MS) resembled MM in the degree of spreading on glass, number of lysosomes, low level of peroxidase and presence of lipid droplets. Intracellular IgA, previously shown to be released from MM (Pittard et al., Ped. Res., vol. 11, No. 4, 721, 1977) was detected by immunofluorescence both in MM and in BM cultured for 24 hours in MS.

Specific lethality of silica for human peripheral blood mononuclear phagocytes, in vitro

Human peripheral blood mononuclear cells, cultured in the presence of 100 μm/ml protein-coated silica particles, were studied to determine changes in number and function of monocytes, immunoglobulin bearing (B), sheep red blood cell rosetting (T) lymphocytes and the effector cells of antibody dependent cell-mediated cytoxicity (ADCC) After 24–48 h, phagocytic cells were effectively eliminated from culture but there was no significant reduction in number or function of T or B lymphocytes or in ADCC to cell line targets. ADCC to erythrocyte targets was inhibited but not completely blocked. It is concluded that silica is a specific toxin for human peripheral blood mononuclear phagocytes and may be useful in in vitro immunological studies as a means of eliminating or determining the role of these cells without resort to separation methods which result in losses of cells other than monocytes.