Respiratory syncytial virus (RSV) is the major viral cause of severe pulmonary disease in young infants worldwide. However, the mechanisms by which RSV causes disease in humans remain poorly understood. To help bridge this gap, we developed an ex vivo/in vitro model of RSV infection based on well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs), the primary targets of RSV infection in vivo. Our RSV/WD-PBEC model demonstrated remarkable similarities to hallmarks of RSV infection in infant lungs. These hallmarks included restriction of infection to noncontiguous or small clumps of apical ciliated and occasional nonciliated epithelial cells, apoptosis and sloughing of apical epithelial cells, occasional syncytium formation, goblet cell hyperplasia/metaplasia, and mucus hypersecretion. RSV was shed exclusively from the apical surface at titers consistent with those in airway aspirates from hospitalized infants. Furthermore, secretion of proinflammatory chemokines such as CXCL10, CCL5, IL-6, and CXCL8 reflected those chemokines present in airway aspirates. Interestingly, a recent RSV clinical isolate induced more cytopathogenesis than the prototypic A2 strain. Our findings indicate that this RSV/WD-PBEC model provides an authentic surrogate for RSV infection of airway epithelium in vivo. As such, this model may provide insights into RSV pathogenesis in humans that ultimately lead to successful RSV vaccines or therapeutics.

Prostasomes may play a complementary role to other immunosuppressive factors contained in the human semen. They may protect sperm cells from deleterious effects of phagocytosing cells, prolong their life, and consequently enhance the chance of conception. At the same time prostasomes may have a permissive effect on sexually transmitted diseases.

There is a need for reproducible and effective models of pediatric bronchial epithelium to study disease states such as asthma. We aimed to develop, characterize, and differentiate an effective, an efficient, and a reliable three-dimensional model of pediatric bronchial epithelium to test the hypothesis that children with asthma differ in their epithelial morphologic phenotype when compared with nonasthmatic children. Primary cell cultures from both asthmatic and nonasthmatic children were grown and differentiated at the air-liquid interface for 28 d. Tight junction formation, MUC5AC secretion, IL-8, IL-6, prostaglandin E2 production, and the percentage of goblet and ciliated cells in culture were assessed. Well-differentiated, multilayered, columnar epithelium containing both ciliated and goblet cells from asthmatic and nonasthmatic subjects were generated. All cultures demonstrated tight junction formation at the apical surface and exhibited mucus production and secretion. Asthmatic and nonasthmatic cultures secreted similar quantities of IL-8, IL-6, and prostaglandin E2. Cultures developed from asthmatic children contained considerably more goblet cells and fewer ciliated cells compared with those from nonasthmatic children. A well-differentiated model of pediatric epithelium has been developed that will be useful for more in vivo like study of the mechanisms at play during asthma. (Pediatr Res 67: 17-22, 2010)

SUMMARYNumerous reports have ascribed immunosuppressive activity to human seminal plasma and there is growing agreement ihat much of this activity can be accounted for by the very high levels of E series prostaglandins present (up to 300 /iM 19-hydroxy prostaglandin E). However not all suppressive activity is due to prostaglandin since several reports have appeared of high molecular weight active substances and we have found that stripped seminal plasma is slill effective in inhibiting the mitogeninduced proliferation of lymphocytes. In this sludy such immunosuppressive activity has been separated by molecular size I'ractionation and the activity has been lound to be particulate and corresponded to the previously reported prostascmes. These are trilaminar to multilaminar vesicles (150 nm diameter) which are secreted by the prostate. Pure preparations of proslasomes inhibited mitogen-induccd lymphoproliferation in a dose-dependont manner with a concentration of prostasomes equivalent to 4{Y'A< of thai seen in seminal fluid giving 69'y,, suppression of thymidine incorporation. The suppressive activity survived boiling and therefore was unlikely ui be due to enzymatic action associated with these organelles. Interaction with Ihe accessory cells, involved in full development ofthe lymphoproliferation induced by mitogen, was indicated and ihis possibility was supported by lhe demonstration ofa direcl effect of prostasomes on macrophage function using a mouse macrophage cell line. The proslasomes in semen may play a complementary role to the prostaglandins in neutralizing the immune defences of the female reproductive tract. This combination would allow the alloantigenie spermatozoa the best chance of achieving fertilization, but at Ihc same time leave the recipient open to any infeetion present in the semen.

SUMMARYDysregulation of IL-6 synthesis is thought to play a role in the development of a number of age-related conditions, such as rheumatoid arthritis, osteoporosis, atherosclerosis, Alzheimer's disease and B cell malignancies. Recently it has been suggested that the production of IL-6 is in¯uenced by the adrenal hormone dehydroepiandrosterone (DHEA) and its sulphated derivative DHEA-S. In humans we investigated the relationship between DHEA-S, IL-6, IL-6 sR and TGF-b1 in the serum of normal healthy male and female blood donors. Using immunoassay techniques we found that the serum levels of DHEA-S signi®cantly (P 0´0001) decreased with age in both males and females. Furthermore, mean DHEA-S levels in all age groups were signi®cantly (P 0´0001) higher in males. Such correlations were not apparent for IL-6 using a standard assay, but a high sensitivity assay revealed that serum IL-6 was signi®cantly (P 0´0018) positively correlated with age in males only. In addition, serum levels of DHEA-S were signi®cantly (P 0´048) negatively correlated with serum IL-6, again in male subjects only. In contrast, serum IL-6 sR and TGF-b1 levels were not correlated with age in either males or females and were not signi®cantly different between the sexes. However, a signi®cant (P 0´024) negative correlation between DHEA-S and IL-6 sR was found in males. These studies clearly highlight the complex nature of the relationship between these molecules in the ageing process in normal healthy blood donors and demonstrate the need to use high sensitivity assays when measuring IL-6 in apparently healthy individuals under the age of 70 years.