What really happens in the neutrophil phagosome?

Current viewpoints concerning the bactericidal mechanisms of neutrophils are reviewed from a perspective that emphasizes challenges presented by the inability to duplicate ex vivo the intracellular milieu. Among the challenges considered are the influences of confinement upon substrate availability and reaction dynamics, direct and indirect synergistic interactions between individual toxins, and bacterial responses to stressors. Approaches to gauging relative contributions of various oxidative and nonoxidative toxins within neutrophils using bacteria and bacterial mimics as intrinsic probes are also discussed.

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► Current views of the modes of neutrophil bactericidal action are summarized.
► Synergistic interactions between microbicidal components are outlined.
► Challenges in extrapolating ex vivo data to intracellular reactions are delineated.
► The use of bacteria as in vivo probes for intraphagosomal reactions is illustrated.