Chemiluminescence Response of Human Natural Killer Cells

Granulocytes and monocytes are known to phagocytose and kill numerous varieties of bacteria and parasites. This function is intimately associated with an early event called the "respiratory burst," which includes the generation of 02and H202 (1). These and other highly reactive molecular species can easily be detected in the presence of luminol or other readily oxidized substrates by the emission of light (chemiluminescence), a phenomenon first described by Allen et al. (2) in reference to phagocytosing neutrophils. The exact mechanism of chemiluminescence is not yet understood (3) but appears related, in part, to species of singlet oxygen and electronically excited carbonyl groups that relax with ensuing light emission (2). The respiratory burst is essential for chemiluminescence because it does not occur in resting cells, in stimulated cells from patients with chronic granulomatous disease, or in normal stimulated cells kept under anaerobic conditions (2, 4, 5). Chemiluminescence is also impaired in myetoperoxidase(MPO) 1 deficient leukocytes or by treatment of cells with heme enzyme inhibitors such as sodium azide (2, 4-6). In addition, phagocytosis-associated chemiluminescence in normal cells is attenuated by both superoxide dismutase (SOD) and catalase (5-7) and is correlated in time with the formation of 02and H202 (8). These and other data indicate that chemiluminescence is dependent on the availability of 02, the activity of the initial oxidase responsible for 02formation, the presence of 02and H202, and the activity of MPO. Microbes are thought to be killed directly by cell-derived H202 and possibly 02and certain free radicals. Tumor cells, on the other hand, are destroyed in part by natural killer (NK) cells (10) in a process that does not involve phagocytosis, much like nonphagocytic killing of tumor cells by maerophages. It has previously been shown that murine macrophages use H202 in their cytolytic mechanism (11), as do human neutrophils (12), but very little is known about the cytolytic mechanism in N K cells. In this paper, we show that the NK-target cell interaction results in an