CHEDIAK-HIGASHI-SYNDROME - QUANTITATION OF A DEFICIENCY IN MAXIMAL BACTERICIDAL CAPACITY

Abstract

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 0.5-65 bacteria per neutrophil, the CHS cells killed normal numbers of bacteria in 60 min. At higher ratios with a mean of 118 bacteria per neutrophil, the percentage of bacteria killed in 60 min 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 min. A H2O2-producing strain of Streptococcus faecalis was killed normally by the CHS neutrophils at 60 min with all ratios of challenge up to 114:1. EM examination of 60-min 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 maximal bactericidal capacity of CHS neutrophils apparently 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.