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Induction of apoptosis of human macrophages in vitro by Legionella longbeachae through activation of the caspase pathway

First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan

Corresponding author: Dr N. Arakaki (e-mail: k970403{at}med.u-ryukyu.ac.jp).

Received 22 Jan. 2001; revised version received 6 Aug. 2001; accepted 14 Aug. 2001.

Abstract

The cytotoxicity of the facultative intracellular bacterium, Legionella longbeachae, an important cause of legionellosis, was characterised. Apoptosis was induced in HL-60 cells, a human macrophage-like cell line, during the early stages of infection and induction of apoptosis correlated with cytotoxicity. Apoptosis was confirmed by agarose gel electrophoresis of fragmented DNA, surface exposure of phosphatidylserine and propidium iodide labelling of host cell nuclei. The involvement of macrophage infectivity potentiator (Mip) protein, a known virulence factor of L. longbeachae, was also examined. A mip mutant of L. longbeachae induced apoptosis of HL-60 cells but failed to multiply intracellularly, suggesting that intracellular replication of L. longbeachae is not essential for the induction of apoptosis of HL-60 cells. Furthermore, induction of apoptosis of L. longbeachae-infected macrophages was mediated by activation of the caspase pathway but might be independent of tumour necrosis factor-- and Fas-mediated signal transduction pathways.

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