UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Neutrophils from patients with heterozygous germline mutations in the von Hippel Lindau protein (pVHL) display delayed apoptosis and enhanced bacterial phagocytosis

Walmsley, SR; Cowburn, AS; Clatworthy, MR; Morrell, NW; Roper, EC; Singleton, V; ... Chilvers, ER; + view all (2006) Neutrophils from patients with heterozygous germline mutations in the von Hippel Lindau protein (pVHL) display delayed apoptosis and enhanced bacterial phagocytosis. BLOOD , 108 (9) 3176 - 3178. 10.1182/blood-2006-04-018796.

Full text not available from this repository.

Abstract

Neutrophils are key mediators of the innate immune response and are required to function at sites of low oxygenation. We have shown that in hypoxia neutrophils are protected from apoptosis via a mechanism dependent on prolyl hydroxylase domain/hypoxia-inducible factor let (PHD/HIF-1 alpha). This response would be predicted to involve the von Hippel Linclau protein (pVHL)-dependent ubiquitination and degradation of HIF-1 alpha. Patients with VHL disease inherit a mutation in one VHL allele, which allows us to study the effects of heterozygous VHL expression in human neutrophils. Neutrophils exhibited a striking "partial hypoxic" phenotype, with delayed rates of apoptosis and enhanced bacterial phagocytosis under normoxic conditions and preserved re-provides direct evidence that the HIF-1 alpha/VHL pathway regulates the innate immune response in humans. It also establishes that heterozygous VHL defects are sufficient to perturb normal responses and illustrates the potential to use this to address the role of HIF and VHL in human biology.

Type:Article
Title:Neutrophils from patients with heterozygous germline mutations in the von Hippel Lindau protein (pVHL) display delayed apoptosis and enhanced bacterial phagocytosis
DOI:10.1182/blood-2006-04-018796
Keywords:PROLYL HYDROXYLASES, AGING NEUTROPHILS, HYPOXIA, HIF, TRANSCRIPTION, INFLAMMATION, HIF-1-ALPHA, EXPRESSION, SURVIVAL
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)

Archive Staff Only: edit this record