ABNORMAL PATTERN OF BACTERICIDAL ACTIVITY OF NEUTROPHILS DEFICIENT IN GRANULES, MYELOPEROXIDASE, AND ALKALINE-PHOSPHATASE

Abstract

The morphology, cytochemistry, metabolism and bactericidal function of neutrophilic polymorphonuclear leukocytes (PMN) from a patient with subacute myelogenous leukemia were evaluated. The patient''s mature PMN were deficient in granules and staining reactivity for myeloperoxidase (MPO) and alkaline phosphatase (LAP). These cells killed Staphylococcus aureus in an abnormal pattern when they were challenged with various increasing multiples of bacteria per neutrophil. At a low ratio of challenge (1.25 bacteria per neutrophil) the MPO-LAP-deficient PMN killed only 18 .+-. 6% (mean .+-. 1 SD) (normal, 79 .+-. 7) of the initial bacterial inoculum. As the PMN were challenged with higher ratios of bacteria/cell, the bactericidal effectiveness of the hypogranular PMN improved. At a 50:1 ratio the patient''s cells killed within the normal range (28 .+-. 10% vs. normal of 48 .+-. 15 [mean .+-. 1 SD]). Although rates of glucose oxidation and O2 consumption by patient or control PMN stimulated with comparable ratios of heat-killed bacteria were the same, only minimal metabolic enhancement was produced in the MPO-LAP-deficient PMN by lower ratios. In contrast, higher ratios produced a marked increase in both of these metabolic activities indicating a major metabolic response to multiple ingestions by the patient''s PMN. These observations may reflect the activation of compensatory microbicidal mechanisms available to the MPO-LAP-deficient PMN only when challenged by large multiples of bacteria.