Cystic Fibrosis Research Today is a free monthly online journal that collates and summarizes the latest research about Cystic Fibrosis, including details on symptoms, genetics, treatment, information.

Profound functional and signaling changes in viable inflammatory neutrophils homing to cystic fibrosis airways.

Tirouvanziam R, Gernez Y, Conrad CK, Moss RB, Schrijver I, Dunn CE, Davies ZA, Herzenberg LA, Herzenberg LA

Departments of Pediatrics, Genetics, and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. tirouvan@stanford.edu

Blood neutrophils recruited to cystic fibrosis (CF) airways are believed to be rapidly killed by resident bacteria and to passively release elastase and other toxic by-products that promote disease progression. By single-cell analysis, we demonstrate that profound functional and signaling changes readily occur within viable neutrophils recruited to CF airways, compared with their blood counterparts. Airway neutrophils have undergone conventional activation, as shown by decreased intracellular glutathione, increased lipid raft assembly, surface mobilization of CD11b+ and CD66b+ granules, and increased levels of the cytoskeleton-associated phospho-Syk kinase. Unexpectedly, they also mobilize to the surface CD63+ elastase-rich granules, usually confined intracellularly, and lose surface expression of CD16 and CD14, both key receptors in phagocytosis. Furthermore, they express CD80, major histocompatibility complex type II, and the prostaglandin D2 receptor CD294, all normally associated with other lineages, which reflects functional reprogramming. This notion is reinforced by their decreased total phosphotyrosine levels, mirroring a postactivated stage, and increased levels of the phospho-S6 ribosomal protein, a key anabolic switch. Thus, we identified a subset of neutrophils within CF airways with a viable but dysfunctional phenotype. This subset provides a possible therapeutic target and indicates a need to revisit current paradigms of CF airway disease.

Published 19 March 2008 in Proc Natl Acad Sci U S A, 105(11): 4335-9.
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