The Chediak-Higashi syndrome: quantitation of a deficiency in maximal bactericidal capacity.
The maximum bactericidal capacity of neutrophils from a patient with the Chediak-Higashi syndrome (CHS) was measured by a quantitative assay in which the neutrophils were challenged with increasing multiples of Staphylococcus aureus, 502A. At various bacterial challenges from 0.5 to 65 bacteria per neutrophil, the CHS cells killed normal numbers of bacteria in 60 minutes. However, at higher ratios with a mean of 118 bacteria per neutrophil, the percentage of bacteria killed in 60 minutes by CHS neutrophils (8.1 +/- 2.3%) was significantly less (P < 0.001) than that killed by normal neutrophils (44 +/- 2.3%). The CHS neutrophils lagged in their ability to kill low challenges of bacteria (0.5 or 1.2 bacteria per neutrophil) only at 20 minutes. A hydrogen-peroxide-producing strain of Streptococcus faecalis was killed normally by the CHS neutrophils at 60 minutes, with all ratios of challenge up to 114 to 1. Electron microscopic examination of 60-minute specimens from high ratios of challenge that were stained for myeloperoxidase activity revealed a failure of many bacteria-laden phagosomes to display this marker of degranulation. The results of this study indicate that the maximal bactericidal capacity of CHS neutrophils is saturated by a significantly lower challenge of bacteria than is required to saturate normal cells. This appears to be the result of sequestration of a significant portion of these cells' bactericidal resources in the giant granules that do not participate appreciably in degranulation.
D000293:Adolescent; D001770:Blood Bactericidal Activity; D002609:Chediak-Higashi Syndrome / Q000097:blood*; D003594:Cytoplasmic Granules / Q000648:ultrastructure; D013293:Enterococcus faecalis; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009504:Neutrophils / Q000502:physiology* / Q000648:ultrastructure; D010587:Phagocytosis; D013211:Staphylococcus aureus; D013997:Time Factors