Genetic disorders of leukocyte function: what they tell us about normal antimicrobial mechanisms of human phagocytic cells.

Abstract

Analysis of three inherited defects of granulocyte function (Chediak-Higashi Syndrome, CHS; Chronic Granulomatous Disease, CGD; Myeloperoxidase Deficiency, MPO) has highlighted critical events for the antimicrobial function of these cells and placed others in perspective. Prompt phagosomal fusion may be more important for digestion of organisms rather than killing as indicated by the mild bactericidal defects in the CHS. The formation of O2- and H2O2 during the phagocytic respiratory burst is central for the broad antimicrobial activity of granulocytes. MPO, on the other hand, while perhaps normally participating in granulocyte antimicrobial action, appears to be essential only for the effective killing of eukaryotic organisms such as certain fungal strains. While the non-oxidative killing mechanism of neutrophils have stimulated much recent interest and were the first to be defined no specific inherited defects have been discovered which are clinically important. Genetic disorders of macrophage effector function remain to be clearly defined as do those of eosinophils. The lessons learned from the study of the granulocyte defects discussed have provided both the technology and approach to the analysis of the antimicrobial and cytocidal mechanisms of these important phagocytic cells.