Human phagocyte respiratory burst by Mycobacterium bovis BCG and M. leprae: functional activation by BCG is mediated by complement and its receptors on monocytes.

We have measured the role of serum components on two parameters of the phagocytosis reaction: a) the chemiluminescence (CL) response associated with the oxidative respiratory burst in response to Mycobacterium bovis BCG and M. leprae, and b) the uptake of these two mycobacteria by healthy human monocytes. Pre-incubations of fresh or heat-inactivated serum or serum containing EGTA or EDTA indicate that these two mycobacteria activate the alternative complement pathway. Monoclonal antibodies against CR1 and CR3 inhibit the responses of M. bovis BCG and M. leprae, demonstrating that complement receptors mediate the phagocytosis of these two mycobacteria. Thus, complement and its receptors on the surface of the monocytes (CR1 and CR3) are important in the functional activation of phagocytosis of M. bovis BCG and M. leprae.

TNF-alpha failed to reverse the M. leprae-induced defective chemiluminescence response of human mononuclear cells.

The effect of phagocyte activation by TNF-alpha on the ability to trigger a chemiluminescence (CL) response, associated with the release of oxidizing species was evaluated in healthy human mononuclear cells in the presence of Mycobacterium leprae. Recombinant TNF-alpha (r-TNF-alpha) increased the CL response of unstimulated M. bovis BCG- and PMA-stimulated cells but did not reverse the M. leprae defective activation of the human phagocyte oxidative burst. M. leprae was less well phagocytosed than M. bovis BCG but phagocytosis of mycobacteria was not altered by addition of r-TNF-alpha. The failure of activation of oxygen-free radical production might have some relevance to the pathogenesis of leprosy.

M. leprae- and BCG-induced chemiluminescence response of monocytes from leprosy patients and healthy subjects: effects of gamma-interferon and GM-CSF.

Mycobacterium leprae, in contrast to BCG, failed to trigger any chemiluminescence (CL) response in mononuclear cells from either leprosy patients or healthy subjects, a deficit not reversed by either interferon-gamma or GM-CSF. Chemiluminescence responses induced without mycobacteria or with BCG were found to be lower in leprosy patients than in controls. M. leprae were also less well phagocytosed than BCG. However, there was a significant difference in phagocytosis between healthy and tuberculoid leprosy subjects. Phagocytosis was not altered by the addition of either lymphokine, and no major differences between healthy subjects and patients were observed. Preincubating mononuclear cells with anti-mycobacteria antibodies (lepromatous patients' sera) did not increase the CL response nor the phagocytosis of M. leprae or BCG.

Phenolic glycolipid-1 from M. leprae inhibits oxygen free radical production by human mononuclear cells.

We studied the effect of PGL1, a phenolic glycolipid unique to Mycobacterium leprae, on the activation of the phagocyte oxidative respiratory burst, by measuring the chemiluminescence (CL) generated by normal mononuclear cells. PGL1 induced a decrease in oxygen free radical production stimulated by mycobacteria (M. leprae, BCG and M. kansasii) or by phorbol myristate acetate, but did not prevent the binding or ingestion of fluorescein-conjugated mycobacteria. In contrast, mycoside A from M. kansasii, a structurally related compound, did not alter the CL response. In addition, treatment of M. leprae with anti-PGL1 antibodies failed to restore the response to this microorganism. PGL1 could act as an oxygen species scavenger and protect M. leprae from killing by toxic oxygen metabolites.

Human phagocyte oxidative burst activation by BCG, M. leprae, and atypical mycobacteria: defective activation by M. leprae is not reversed by interferon gamma.

The activation of the phagocyte oxidative respiratory burst by various mycobacteria was evaluated in an in vitro assay, by measuring the chemiluminescence, associated to the release of oxidizing species, generated by normal human whole blood phagocytes. All mycobacterium species, except Mycobacterium leprae, induced a significant chemiluminescence response. The strongest stimulus was provided by BCG, followed by M. triviale, M. chelonei, and M. fortuitum. M. kansasii, M. intracellulare, and M. lepraemurium elicited a weak response, although higher than that triggered by M. leprae. Both polymorphonuclear and mononuclear cells contributed to the whole blood cell chemiluminescence stimulated by mycobacteria, mononuclear cells being more efficient on a per cell basis. Phagocyte activation by recombinant interferon gamma did not improve M. leprae ability to trigger a significant chemiluminescence response. The failure of M. leprae and of some atypical mycobacteria to stimulate a strong phagocyte oxidative respiratory burst may have some relevance to their pathogenicity.

[Macrophage activation and Mycobacterium leprae: effect of interferon gamma on the production of oxygen free radicals by phagocytic cells]. / Activation macrophagique et Mycobacterium leprae: action de l'interféron gamma sur la production de radicaux oxygénés libres (R.O.L.) des cellules phagocytaires.

Activation of the respiratory metabolic channel (F.O.R.), responsible in part for the bactericidal effect, was measured in vitro by a chemoluminescence test on circulating phagocytes. All mycobacteria tested, except for Mycobacterium leprae, induced a significant response. Its effect on lepromatous leprosy pathology is a subject for discussion.