Leukotriene biosynthesis by polymorphonuclear leukocytes from two patients with chronic granulomatous disease

Area of Science:

• Immunology
• Biochemistry

Background:

• Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by impaired function of phagocytes, particularly neutrophils.
• Phagocytes play a crucial role in host defense through the generation of reactive oxygen species and the production of inflammatory mediators like leukotrienes.

Purpose of the Study:

• To investigate the ability of polymorphonuclear leukocytes (PMNL) from CGD patients to metabolize arachidonic acid into lipoxygenase products, specifically leukotriene B4 (LTB4).
• To determine if the impaired respiratory burst in CGD neutrophils affects arachidonic acid oxidation pathways.

Main Methods:

• PMNL were isolated from two CGD patients and healthy controls.
• Incubations with arachidonic acid and the calcium ionophore A23187 were performed.
• Production of LTB4 and other hydroxy-eicosatetraenoic acids was analyzed.
• PMNL chemiluminescence and generation of active oxygen species were assessed.

Main Results:

• PMNL from CGD patients produced LTB4 and other lipoxygenase products at levels comparable to controls.
• The production of these metabolites occurred even in the absence of detectable superoxide anion generation.
• CGD leukocytes failed to generate active oxygen species in response to stimuli, confirming the disease phenotype.

Conclusions:

• The ionophore-induced production of leukotrienes from arachidonic acid is dissociated from the leukocyte respiratory burst and superoxide anion generation.
• The defect in chronic granulomatous disease does not appear to impair the ability of PMNL to oxygenate arachidonic acid to leukotrienes.