Blockade of IL-33 release and suppression of type 2 innate lymphoid cell responses by helminth secreted products in airway allergy

Helminth parasites such as the nematode Heligmosomoides polygyrus strongly inhibit T helper type 2 (Th2) allergy, as well as colitis and autoimmunity. Here, we show that the soluble excretory/secretory products of H. polygyrus (HES) potently suppress inflammation induced by allergens from the common fungus Alternaria alternata. Alternaria extract, when administered to mice intranasally with ovalbumin (OVA) protein, induces a rapid (1–48 h) innate response while also priming an OVA-specific Th2 response that can be evoked 14 days later by intranasal administration of OVA alone. In this model, HES coadministration with Alternaria/OVA suppressed early IL-33 release, innate lymphoid cell (ILC) production of IL-4, IL-5, and IL-13, and localized eosinophilia. Upon OVA challenge, type 2 ILC (ILC2)/Th2 cytokine production and eosinophilia were diminished in HES-treated mice. HES administration 6 h before Alternaria blocked the allergic response, and its suppressive activity was abolished by heat treatment. Administration of recombinant IL-33 at sensitization with Alternaria/OVA/HES abrogated HES suppression of OVA-specific responses at challenge, indicating that suppression of early Alternaria-induced IL-33 release could be central to the anti-allergic effects of HES. Thus, this helminth parasite targets IL-33 production as part of its armory of suppressive effects, forestalling the development of the type 2 immune response to infection and allergic sensitization

Lung epithelium as a sentinel and effector system in pneumonia – molecular mechanisms of pathogen recognition and signal transduction

Pneumonia, a common disease caused by a great diversity of infectious agents is responsible for enormous morbidity and mortality worldwide. The bronchial and lung epithelium comprises a large surface between host and environment and is attacked as a primary target during lung infection. Besides acting as a mechanical barrier, recent evidence suggests that the lung epithelium functions as an important sentinel system against pathogens. Equipped with transmembranous and cytosolic pathogen-sensing pattern recognition receptors the epithelium detects invading pathogens. A complex signalling results in epithelial cell activation, which essentially participates in initiation and orchestration of the subsequent innate and adaptive immune response. In this review we summarize recent progress in research focussing on molecular mechanisms of pathogen detection, host cell signal transduction, and subsequent activation of lung epithelial cells by pathogens and their virulence factors and point to open questions. The analysis of lung epithelial function in the host response in pneumonia may pave the way to the development of innovative highly needed therapeutics in pneumonia in addition to antibiotics

Decay of tungsten-189

WOS: 000178847900005PubMed ID: 12433036We studied the decay of W-189 as produced via the Os-192[n,alpha]W-189 reaction on a 99.9% isotopically enriched Os-192 target. The irradiations were performed at the intense neutron beam facility at Cyclotron Research Center, Universite Catholique Louvain-la-Neuve(CRC-UCL) (Belgium), where fast neutrons [E-n similar to20MeV, phi(n) = (4.8+/-0.3)10(11) ns(-1) cm(-2)] were generated by stopping 50 MeV deuterons on a thick Be target. The half-life of W-189 was determined to be 9.3+/-0.3min, compared to 10.8+/-0.2min obtained from the W-188[n,gamma]W-189 reaction. The energies of the two predominant gamma-rays of W-189, 260.4+/-1.3 and 421.7+/-1.4 keV were in good agreement with that from the [n,gamma] reaction, however, the relative intensities of the two T-rays were not consistent. From the [n,] reaction, the relative intensities of the 260 and 421 keV gamma-rays were 97 to 100, whereas from the [n,alpha] reaction the relative intensities were 100 to 77, respectively. Assuming a cross-section ratio of 20+/-5 for [n,p3n] to [n,alpha] reactions, a cross-section of 0.5+/-0.2 mb was suggested for the Os-192[n,alpha]W-189 reaction, and the absolute intensity of the 260 keV gamma-ray was estimated to be similar to50%. (C) 2002 Elsevier Science Ltd. All rights reserved

Labeling of acetaminophen with I-131 and biodistribution in rats

WOS: 000235852700021PubMed ID: 16462075The aim of the present study was to label acetaminophen (APAP) with I-131 and to determine its radiopharmaceutical potential in rats. Acetaminophen was labeled with I-131 using the iodogen method. The radiochemical purity of I-131-APAP was determined by RTLC and paper electrophoresis. The labeling yield was 94 +/- 4%. The biodistribution studies of the labeled compound (specific activity; 56.60 GBq/mmol) were performed in male Albino Wistar rats. The uptake of I-131-APAP in some organs were determined at different time after injection to the rats. The radioactivity in each organ was counted and the percentage of injected activity per gram of tissue weight (%ID/g) for each organ and blood was calculated. I-131-APAP uptake in the lung, liver, kidneys, pancreas, blood, stomach and some brain region, were observed. Thus, I-131-APAP may be radiopharmaceutical for the imaging of the brain

Labeling of famotidine with Tc-99m and biodistribution studies on rats

WOS: 000223119100012Famotidine, a gastrointestinal drug was labeled with Tc-99m and its radiopharmaceutical potential was observed on male Albino Wistar rats. Labeling yield was over 95%. Average specific activity and n-octanol/water partition coefficient (lipophilicity) were approximately 74 MBq/mg-0.66 GBq/mg and 3.4, respectively. Biodistribution studies were performed on Albino Wistar rats. The activity per gram tissue was calculated and time activity curves were generated. The majority of the activity was observed in stomach, small intestines and kidneys. Liver and kidneys showed lower uptake compared to other H-2-receptor rich tissues. Results show that Tc-99m-famotidine is H-2 receptor specific