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Intracellular multiplication of Legionella pneumophila in HL‐60 cells differentiated by 1,25‐dihydroxyvitamin D3 and the effect of interferon y
Author(s) -
Watanabe Masayuki,
Shimamoto Yoshinori,
Yoshida Shinichi,
Suga Kenji,
Mizuguchi Yasuo,
Kohashi Osamu,
Yamaguchi Masaya
Publication year - 1993
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.54.1.40
Subject(s) - biology , legionella pneumophila , intracellular , microbiology and biotechnology , antigen , monocyte , immunology , bacteria , genetics
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 γ (IFN‐γ) 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 10‐6M 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‐7 for 1‐24 h (γ‐IFN‐D3‐HL‐60 cells) before infection markedly inhibited L. pneumophila multiplication, the effect of IFN‐γ being dose dependent. Surface marker analysis was carried out in HL‐60, D3‐HL‐60, and 7‐IFN‐D3‐HL‐60 cells. On D3‐HL‐60 cells, CDllb, CDllc, 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, CDllb(CR3) and CD35(CR1), seemed to be important for phagocytosis and for the subsequent intracellular multiplication of L. pneumophila. The γ‐IFN‐ D3‐HL‐6O 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‐γ to markedly inhibit bacterial growth.