- Volume 58 , Number 2
- Page: 389
Macrophage microbicidal mechanism
To the Editor:
Jolly and Mahadevan have attempted to study the role of reactive oxygen intermediates in the intracellular killing of Mycobacterium leprae in human macrophages (3). The authors have reported 89 nmol of H2O2 and 0.3 nmol of superoxide (O2) in the macrophages of lepromatous leprosy patients.
During phagocytosis, macrophages produce substantial quantities of O
and H2O2 as shown by the following reactions: Superoxide is formed by the one electron reduction of oxygen: 2O2 + NADPH → O2 + NADP+ + H+. Superoxide is converted to H2O2 by the reaction 2O2 + 2H+ → O2 + H2O2. This reaction is catalyzed by the enzyme superoxide dismutase.
Considering the fact that all of the oxygen taken up during the respiratory burst is converted to O , and that 80% of this O is converted to H2O2 by dismutation (1), it is difficult to understand from the paper how 89 nmol H2O2 could be accounted for when only 0.3 nmol O was produced (Table 1).
However, there is a report which claims a direct conversion of molecular oxygen to H2O2 (2), as shown by the reaction: NADH + O2 + H+ → H2O2 + NAD+. This has been reported in guinea-pig neutrophils in vitro. It has also been argued that the rather high Km (0.4 mM) for NADH observed in vitro for this enzyme militates against significant activity during phagocytosis (2).
Under these circumstances, more confirmation is needed regarding the role of superoxide and H2O2 in the killing of M. leprae by human macrophages.
- Raji Swamy, M.D., Ph.D.
Department of Immunology
Tuberculosis Research Centre
Spur Tank Road
Chetput, Madras 600031, India
REFERENCES
1. Babior, B. M. Oxygen dependent microbial killing by phagocytes. N. Engl. J. Med. 298(1978)659-668.
2. Badwey, J. A. and Karnavsky, M. L. Active oxygen species of the functions of phagocytic leukocytes. Ann. Rev. Biochem. 49(1980)695-726.
3. Jolly. M. and Mahadevan, P. R. Reactive oxygen intermediates inactivate Mycobacterium leprae in the phagocytes from human peripheral blood. Int. J. Lepr. 57(1989)483-491.