Optimal complement-mediated phagocytosis of Pseudomonas aeruginosa by monocytes is cystic fibrosis transmembrane conductance regulator-dependent.

Cystic fibrosis (CF) is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and is characterized by chronic pulmonary infections. The mechanisms underlying chronic infection and inflammation remain incompletely understood. Mutant CFTR in nonepithelial tissues such as immune cells has been suggested to contribute to infection, inflammation, and the resultant lung disease. However, much controversy still exists regarding the intrinsic role of CFTR in immune cells, especially phagocytes. Therefore, we investigated CFTR expression and function in neutrophils and monocytes isolated from human peripheral blood. CFTR function was assessed by comparing non-CF and CF cells, before and after the chemical inhibition of CFTR. We found CFTR protein expression in monocytes, but this expression was limited or undetectable in neutrophils. Furthermore, the phagocytosis and intracellular killing of Pseudomonas aeruginosa was reduced in CF monocytes, and impaired phagocyte effector mechanisms were phenocopied in non-CF monocytes upon the pharmacological inhibition of CFTR. Reduced phagocytosis in CF monocytes relied on the complement-dependent opsonization of Pseudomonas aeruginosa, and was also observed in the context of latex particles labeled with purified C3b. In mechanistic terms, we observed that CFTR function in monocytes is required for the optimal expression of CD11b. We observed no role for CFTR in neutrophil-mediated phagocytosis. These data support an intrinsic role for CFTR in monocytes, and suggest that CFTR-dependent alterations in complement-mediated interactions between Pseudomonas aeruginosa and monocytes may contribute to enhanced susceptibility to infection in patients with CF.

Effects of Aspergillus fumigatus colonization on lung function in cystic fibrosis.

PURPOSE OF REVIEW: Aspergillus fumigatus is frequently isolated from cystic fibrosis (CF) patients and is notorious for its role in the debilitating condition of allergic bronchopulmonary aspergillosis (ABPA). Although CF patients suffer from perpetual microorganism-related lung disease, it is unclear whether A. fumigatus colonization has a role in causing accelerated lung function decline and whether intervention is necessary. RECENT FINDINGS: A. fumigatus morbidity appears to be related to cystic fibrosis transmembrane conductance regulator-dependant function of the innate immune system. A. fumigatus-colonized patients have a lower lung capacity, more frequent hospitalizations and more prominent radiological abnormalities than noncolonized patients. Treatment with antifungal agents can be of value but has several drawbacks and a direct effect on lung function is yet to be shown. SUMMARY: A. fumigatus appears to have an important role in CF lung disease, not exclusive to the context of ABPA. However, a causal relationship still needs to be confirmed. Study observations and trends indicate a need to further elucidate the mechanisms of A. fumigatus interactions with the host innate immune system and its role in CF lung morbidity.

Semen donors' curiosity about donor offspring and the barriers to their knowing.

The article reports qualitative research findings which explored the meanings of kinship and genetic knowledge of fifteen pre-1990 semen donors in the UK. This is presented in the context of public and academic debates about the regulation of access to genetic information, genetic information as intellectual property and kinship knowledge, and the multiple ownership of genetic information. Semen donors in the UK traditionally were expected to take no interest in what became of their donations and those who did were considered to be unsuitable as donors. However, the present research reveals that men who donated in the past hold varied attitudes, including curiosity about how donor offspring have fared and what they look like. Whilst some donors would welcome direct contact with donor offspring, there are practical and emotional obstacles to satisfying their curiosity. Donors' views reflect the varied understandings in the UK about the implications of genetic relatedness and the time and energy required to maintain and sustain relationships.