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Abnormal pattern of bactericidal activity of neutrophils deficient in granules, myeloperoxidase, and alkaline
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 per cent (mean +/- 1 S.D.) (normal, 79 +/- 7) of the initial bacterial inoculum. As the PMN were challenged with higher ratios of bacteria per 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 per cent vs. normal of 48 +/- [mean +/- 1 S.D.]). Although rates of glucose oxidation and oxygen 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.
Insights
Neutrophilic polymorphonuclear leukocytes (PMN) from a leukemia patient showed impaired bacterial killing due to myeloperoxidase (MPO) and alkaline phosphatase (LAP) deficiency. Their function improved only when challenged with high bacteria multiples, suggesting compensatory mechanisms.
Area of Science:
- Hematology
- Immunology
- Cell Biology
Background:
- Subacute myelogenous leukemia can affect neutrophil function.
- Neutrophilic polymorphonuclear leukocytes (PMN) are critical for innate immunity.
- Myeloperoxidase (MPO) and alkaline phosphatase (LAP) are key enzymes in PMN bactericidal activity.
Observation:
- Patient's mature PMN exhibited granule deficiency and reduced MPO/LAP reactivity.
- Bacterial killing of Staphylococcus aureus by patient's PMN was significantly impaired at low bacteria-to-neutrophil ratios.
- Hypogranular PMN demonstrated improved bactericidal effectiveness at higher bacterial challenge ratios.
Findings:
- MPO-LAP-deficient PMN killed only 18% of bacteria at a 1.25:1 ratio, compared to 79% in normal PMN.
- At a 50:1 ratio, patient's PMN killing improved to 28%, nearing the normal range (48%).
- Metabolic activity (glucose oxidation, oxygen consumption) showed minimal enhancement at low ratios but marked increase at high ratios in MPO-LAP-deficient PMN.
Implications:
- Deficient PMN function in leukemia can be compensated by high bacterial loads.
- Suggests activation of alternative microbicidal mechanisms in MPO-LAP-deficient PMN under stress.
- Highlights the complex interplay between neutrophil enzyme deficiencies and host defense strategies.