Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined leukemic cells, HL-60, an acute promyelocytic leukemia cell line, after differentiation induced by 1,25-dihydroxyvitamin D3 (D3) and retinoic acid (A) for infection of Legionella pneumophila, the etiologic agent of Legionnaires' disease. We investigated the effect of interferon gamma (IFN-gamma) on the differentiated cells and on the intracellular growth of the bacteria. An examination of morphological and antigenic changes in the cells was also included in the study. After 4-day incubation with 10(-6)M D3 or A, the HL-60 cells differentiated into monocyte-like (D3-HL-60) or mature granulocyte-like (A-HL-60) cells, respectively. They were then infected with L. pneumophila. Intracellular multiplication of the bacteria was evident in D3-HL-60 cells but not in HL-60 or A-HL-60 cells. D3-HL-60 cells required a 24-h infection time for the intracellular growth of L. pneumophila. D3-HL-60 cells activated with human recombinant IFN-gamma for 1-24 h (gamma-IFN-D3-HL-60 cells) before infection markedly inhibited L. pneumophila multiplication, the effect of IFN-gamma being dose dependent. Surface marker analysis was carried out in HL-60, D3-HL-60, and gamma-IFN-D3-HL-60 cells. On D3-HL-60 cells, CD11b, CD11c, CD14, and CD35 antigen increased, whereas CD71 and HLA-DR antigen decreased. This finding suggested that HL-60 cells differentiated into monocyte-like cells; the acquisition of the complement receptors, CD11b(CR3) and CD35(CR1), seemed to be important for phagocytosis and for the subsequent intracellular multiplication of L. pneumophila. The gamma-IFN-D3-HL-60 cells showed an increase of CD16, CD36, CD71, and HLA-DR antigen, suggesting that they were in an activated state. Our study indicated, first, that D3 can induce human leukemic cells to differentiate into functional monocyte-macrophage-like cells that can support the intracellular multiplication of L. pneumophila and, second, that these differentiated leukemic cells can be activated by IFN-gamma to markedly inhibit bacterial growth.
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PMID:Intracellular multiplication of Legionella pneumophila in HL-60 cells differentiated by 1,25-dihydroxyvitamin D3 and the effect of interferon gamma. 833 78

Legionella pneumophila is a facultative intracellular pathogen that parasitizes host mononuclear phagocytes. Cell-mediated immunity is pivotal to host defense against L. pneumophila, and the infected host cell may play a central role in processing and presenting parasite antigens to lymphocytes mediating cell-mediated immune response. However, in the case of L. pneumophila and intracellular parasites in general, little is known about the intracellular trafficking of parasite antigens, the influence of parasite infection on major histocompatibility complex (MHC) expression, or the relationship of MHC molecules to sites of parasite replication. To learn more about this, we have used flow cytometry to study the expression of HLA-DR by monocytes infected with L. pneumophila and cryosection immunogold electron microscopy to study the distribution of MHC class I and II molecules on L. pneumophila phagosomes. Flow cytometry analysis demonstrated that L. pneumophila infection has little effect on the overall expression of HLA-DR by monocytes. Cryosection immunogold studies revealed abundant staining for MHC class I and II molecules on the plasma membrane of infected monocytes but little or no staining on the membranes of mature L. pneumophila phagosomes. Cryosection immunogold studies of an avirulent mutant of L. pneumophila that, unlike the wild type, does not inhibit phagosome-lysosome fusion and subsequently survives but does not multiply in a phagolysosome yielded similar results. We have previously found that MHC class I and II molecules are excluded from nascent phagosomes during coiling and conventional phagocytosis. The present work demonstrates that MHC molecules do not accumulate appreciably in the L. pneumophila phagosome as it matures and at a point in the life cycle of the organism in which it is replicating and producing immunoprotective T-cell antigens. This suggests that L. pneumophila does not reside in a typical endosomal compartment in the host cell and that L. pneumophila antigens may encounter MHC molecules at extraphagosomal sites within the host cell.
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PMID:Hypoexpression of major histocompatibility complex molecules on Legionella pneumophila phagosomes and phagolysosomes. 851 82

The differentiation of HL-60, a human leukemic cell line, into monocyte-like cells (D3-HL-60 cells) is induced by 1,25-dihydroxyvitamin D3 (D3). We examined the effects of interferon (IFN) treatment of D3-HL-60 cells on the expression of cell surface antigens, the phagocytic activity for fluorescent beads, production of oxygen radicals, and intracellular growth of Legionella pneumophila. Activation of D3-HL-60 cells with IFN-gamma, Beta, and alpha for 24 h significantly increased expression of CD16, CD36, CD71, and HLA-DR antigens. IFN-gamma markedly enhanced the phagocytic activity of beads in D3-HL-60 cells. There was no significant difference in phagocytic activity between cells exposed to IFN-alpha or beta and untreated D3-HL-60 cells. IFN-alpha, beta, and gamma enhanced production of oxygen radicals, including superoxide, by D3-HL-60 cells. Superoxide production was enhanced to the greatest degree by IFN-gamma, followed by IFN-beta and then IFN-gamma. Intracellular growth of L. pneumophila in D3-HL-60 cells was inhibited by interferons (IFN-gamma > beta > gamma). Similar results were obtained in human mononuclear cells. These data indicate that interferons can act as biologic response modifiers not only in human mononuclear cells but also in differentiated leukemic cells. Our results may have implications for the development of differentiation therapy for treatment of leukemia.
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PMID:Effects of interferon-alpha, beta, and gamma on the function of differentiated leukemic HL-60 cells induced by 1,25-dihydroxyvitamin D3. 872 74