Neutrophil Dysfunction in the Pathogenesis of Cystic Fibrosis (CF) – Physician’s Weekly

Polymorphonuclear neutrophils (PMNs) play an important role in both host defense and noninfectious inflammation. Failure to stop the inflammatory response and its causes can feed the excessive inflammation seen in many human disorders, including cystic fibrosis (CF), an autosomal recessive genetic disease caused by mutations in the CF transmembrane conductance regulator. For a study, researchers focused on the molecular basis for, and clinical repercussions of, abnormalities in the MPO-H2O2-Cl system caused by CFs impaired Cl transport. They first discussed how the MPO-H2O2-Cl system participates in host defense and inflammation resolution in healthy PMNs, and then looked at how a defective MPO-H2O2-Cl system contributes to the increased susceptibility to infection and dysregulated inflammation associated with CF clinical manifestations.

Multiple end organs are affected by CF, with persistent bacterial infection and chronic neutrophilic inflammation in the airways dominating the clinical picture. PMNs have a number of antimicrobial mechanisms to delay or kill invading microorganisms contained in their phagosomes to fit the varied microbial challenges that they may face. PMN defense systems are notable for their capacity to produce hypochlorous acid, a powerful microbicide, by combining oxidants produced by the NADPH oxidase with myeloperoxidase (MPO) released from azurophilic granules in the presence of chloride (Cl). MPO-H2O2-Cl system products oxidize sensitive biomolecules and promote powerful antibacterial activity against many, but not all, potential human infections.

Individuals with defects in any component of the MPO-H2O2-Cl system, as seen in chronic granulomatous disease of MPO deficiency, have increased rates or severity of infection and signs of dysregulated inflammatory responses, highlighting the importance of the MPO-H2O2-Cl system in optimal host defense and proper regulation of inflammation.

Reference:ashpublications.org/blood/article-abstract/139/17/2622/484179/Neutrophil-dysfunction-in-the-pathogenesis-of?redirectedFrom=fulltext

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Neutrophil Dysfunction in the Pathogenesis of Cystic Fibrosis (CF) - Physician's Weekly