Neutrophil Activity in Chronic Granulomatous Disease

Abstract

The killing of microorganisms by neutrophils causes degranulation of azurophilic, specific, and gelatinase granules into the formed phagolysosomes. During the degranulation process, increased surface expression of CD63 (localized in the azurophilic granules of resting neutrophils) and CD66b/CD67 (from specific granules) can be detected. This results from the fusion of the granule membrane, containing these markers, with a plasma membrane. Release of granule content into the phagolysosomes or the extracellular environment occurs not only upon proper cell activation but also upon tissue injury. We compared expression of degranulation markers on neutrophils from chronic granulomatous disease (CGD) patients and healthy volunteers. Surface expression of CD63 in non-stimulated and phorbol 12-myristate 13-acetate (PMA)-stimulated neutrophils, bactericidal activity of serum, and alpha-defensins level (HNP 1–3) in plasma of CGD patients were significantly higher in comparison with healthy volunteers. At the same time, the levels of intracellular HNP 1–3 in CGD neutrophils were lower than in normal neutrophils. Thus, our data revealed augmented degranulation of azurophilic neutrophil granules in CGD, which might play a role in tissue destruction observed in this disease.