SUMMARY Endothelins (ET) are a family of regulatory peptides displaying, among other abilities, p... more SUMMARY Endothelins (ET) are a family of regulatory peptides displaying, among other abilities, potent constrictor actions. We studied the perinatal time course expression and distribution of ET in the mouse airway epithelium. In fetal mouse, ET-immunoreactivity (IR) appeared earlier (gestational Day 18) in the epithelium of upper (bronchi and large bron- chioles) than in lower airways, being scarce and mainly
The mechanisms by which Foxp3+ T regulatory cells (Treg) accumulate in HCV infected livers are no... more The mechanisms by which Foxp3+ T regulatory cells (Treg) accumulate in HCV infected livers are not known. Here, we studied the role of chemokines CCL17 and CCL22 in this process. Chemokine mRNA levels were determined by qPCR in liver biopsies from 26 HCV chronically infected patients (CHC), 11 patients with treatment-induced sustained virological response (SVR), 16 patients with other liver diseases unrelated to HCV, and 24 normal livers. Double-immunofluorescence Foxp3/CD3 or CD11c/CCL22 was performed in liver sections. Chemokine production by monocyte-derived dendritic cells (MDDC) co-cultured with uninfected or HCV-JFH1 infected Huh7 cells was measured by qPCR and ELISA. Chemotactic activity of culture supernatants was also tested. Foxp3+ Treg were increased in CHC livers as compared to controls. Patients with CHC showed elevated intrahepatic levels of CCL17 mRNA compared to normal livers or livers from subjects with SVR or other forms of liver disease. Intrahepatic CCL22 expression was also higher in CHC than in healthy subjects or SVR patients but similar to that observed in other liver diseases. Dendritic cells producing CCL22 could be found inside the hepatic lobule in CHC patients. Contact between MDDC and HCV-JFH1-infected Huh7 cells induced the expression of CCL17 and CCL22 in a process partially dependent on ICAM-1. Transwell experiments showed that upregulation of these chemokines enhanced Treg migration. Contact of HCV-infected cells with dendritic cells induces the production of Treg-attracting chemokines, an effect which may favour liver accumulation of Treg in CHC. Our findings contribute to explain the mechanism by which HCV escapes the immune response and thus reveals novel therapeutic targets.
The gastrointestinal tract (GIT) appears to be the main site of entry for the pathological isofor... more The gastrointestinal tract (GIT) appears to be the main site of entry for the pathological isoform of prions (PrP(sc)). To understand how the PrP(sc) internalization process occurs, it is important to characterize the cell types that express normal prion protein (PrP(c)) along the GIT. To do so, we studied the distribution of PrP(c) in the rat, monkey, and cow GIT. Using Western blot analysis, we found that PrP(c) is expressed in all digestive regions of the three species. Immunoreactivity for PrP(c) was found throughout the GIT in epithelial cells sharing the neuroendocrine (NE) phenotype. Immunostained cells appeared scattered throughout the epithelium of fundic and pyloric glands as well as in intestinal villi and crypts.
The gastrointestinal tract (GIT) is one of the most likely entry sites for the pathological isofo... more The gastrointestinal tract (GIT) is one of the most likely entry sites for the pathological isoform of prions (PrP(sc)). To understand how PrP(sc) crosses the digestive mucosa, it is crucial to characterize the cells expressing normal prion protein (PrP(c)). By means of double immunofluorescence applied to sections of the monkey GIT, we demonstrated that, in the stomach, PrP(c) immunostaining occurs in subsets of histamine, somatostatin (Som), ghrelin (Ghr), gastrin (G), and serotonin (5HT) cells. In the small and large bowels, PrP(c) cells were found in subpopulations of cells immunolabeled for 5HT, Som, G, and peptide YY (PYY).
ABSTRACT Among the different cell types present in the respiratory tract of the vertebrates, some... more ABSTRACT Among the different cell types present in the respiratory tract of the vertebrates, some (epithelial, endothelial, neural) specialise in the production of regulatory factors. Endocrine cells occur either single, spread throughout the epithelial lining, or in innervated groups, called 'neuroepithelial bodies' (NEBs). In mammals, these endocrine cells may be involved in lung maturation during perinatal life and in chemoreception. A neuroendocrine diffuse system is present in the respiratory organs of all classes of vertebrates. In amphibians and reptiles, single endocrine cells as well as NEBs are located in the apices of the lung septa. The respiratory tract shows nerve fibres immunoreactive to several neuropeptides. Since some neurons and fibres contain NO synthase a broad evolutionary presence of NO-releasing neurons, probably involved in the control of relaxation, is suggested.
American Journal of Respiratory Cell and Molecular Biology, 1999
Several studies, including histochemical ones, have indicated that nitric oxide (NO) of endotheli... more Several studies, including histochemical ones, have indicated that nitric oxide (NO) of endothelial origin may be related to the pulmonary vasodilation that occurs at birth. Since no histologic studies have been done of the possible parallel perinatal increase in production of neuronal NO synthase (nNOS) by pulmonary nerve plexuses, we investigated the distribution of nNOS in fetal, neonatal, and adult mouse lung. Lungs from mice aged 13 d gestation to 6 d after birth and lungs of adults were studied through histochemistry for nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity and immunocytochemistry. Both techniques gave almost similar results in relation to time of appearance, distribution, and frequency of neural structures positive for NADPH-d and NOS. NADPH-d staining was also applied to whole mounts of developing and adult tracheae. Staining was found from gestational days 13 to 15 onward in a small portion of the neuronal population. In all stages studied, NADPH-d/NOS staining was found in neuron cell bodies in the hilar region and bronchiolar wall, as well as in neuronal processes. Labeled terminal nerve fibers with varicosities were more frequent in pulmonary blood vessels than in airways. In tracheae, similar NADPH-d/NOS-positive nerve plexuses were found. The presence of nNOS in fetal and neonatal mouse respiratory tract suggests that neurally derived NO must play a role in developing lung physiology. However, because no perinatal increase in the number or intensity of staining of nNOS-positive nerve structures was seen, no apparent relation between neural NO and vasodilation can be established at birth.
Journal of Hepatology, Volume 44, Issue null, Pages S198, April 2006, Authors:E. Larrea; JI Riezu... more Journal of Hepatology, Volume 44, Issue null, Pages S198, April 2006, Authors:E. Larrea; JI Riezu-Boj; L. Gil-Guerrero; N. Casares; R. Aldabe; P. Sarobe; MP Civeira; J. Quiroga; L. Guembe; F. Borrás-Cuesta; JJ Lasarte; J. Prieto.
SUMMARY Endothelins (ET) are a family of regulatory peptides displaying, among other abilities, p... more SUMMARY Endothelins (ET) are a family of regulatory peptides displaying, among other abilities, potent constrictor actions. We studied the perinatal time course expression and distribution of ET in the mouse airway epithelium. In fetal mouse, ET-immunoreactivity (IR) appeared earlier (gestational Day 18) in the epithelium of upper (bronchi and large bron- chioles) than in lower airways, being scarce and mainly
The mechanisms by which Foxp3+ T regulatory cells (Treg) accumulate in HCV infected livers are no... more The mechanisms by which Foxp3+ T regulatory cells (Treg) accumulate in HCV infected livers are not known. Here, we studied the role of chemokines CCL17 and CCL22 in this process. Chemokine mRNA levels were determined by qPCR in liver biopsies from 26 HCV chronically infected patients (CHC), 11 patients with treatment-induced sustained virological response (SVR), 16 patients with other liver diseases unrelated to HCV, and 24 normal livers. Double-immunofluorescence Foxp3/CD3 or CD11c/CCL22 was performed in liver sections. Chemokine production by monocyte-derived dendritic cells (MDDC) co-cultured with uninfected or HCV-JFH1 infected Huh7 cells was measured by qPCR and ELISA. Chemotactic activity of culture supernatants was also tested. Foxp3+ Treg were increased in CHC livers as compared to controls. Patients with CHC showed elevated intrahepatic levels of CCL17 mRNA compared to normal livers or livers from subjects with SVR or other forms of liver disease. Intrahepatic CCL22 expression was also higher in CHC than in healthy subjects or SVR patients but similar to that observed in other liver diseases. Dendritic cells producing CCL22 could be found inside the hepatic lobule in CHC patients. Contact between MDDC and HCV-JFH1-infected Huh7 cells induced the expression of CCL17 and CCL22 in a process partially dependent on ICAM-1. Transwell experiments showed that upregulation of these chemokines enhanced Treg migration. Contact of HCV-infected cells with dendritic cells induces the production of Treg-attracting chemokines, an effect which may favour liver accumulation of Treg in CHC. Our findings contribute to explain the mechanism by which HCV escapes the immune response and thus reveals novel therapeutic targets.
The gastrointestinal tract (GIT) appears to be the main site of entry for the pathological isofor... more The gastrointestinal tract (GIT) appears to be the main site of entry for the pathological isoform of prions (PrP(sc)). To understand how the PrP(sc) internalization process occurs, it is important to characterize the cell types that express normal prion protein (PrP(c)) along the GIT. To do so, we studied the distribution of PrP(c) in the rat, monkey, and cow GIT. Using Western blot analysis, we found that PrP(c) is expressed in all digestive regions of the three species. Immunoreactivity for PrP(c) was found throughout the GIT in epithelial cells sharing the neuroendocrine (NE) phenotype. Immunostained cells appeared scattered throughout the epithelium of fundic and pyloric glands as well as in intestinal villi and crypts.
The gastrointestinal tract (GIT) is one of the most likely entry sites for the pathological isofo... more The gastrointestinal tract (GIT) is one of the most likely entry sites for the pathological isoform of prions (PrP(sc)). To understand how PrP(sc) crosses the digestive mucosa, it is crucial to characterize the cells expressing normal prion protein (PrP(c)). By means of double immunofluorescence applied to sections of the monkey GIT, we demonstrated that, in the stomach, PrP(c) immunostaining occurs in subsets of histamine, somatostatin (Som), ghrelin (Ghr), gastrin (G), and serotonin (5HT) cells. In the small and large bowels, PrP(c) cells were found in subpopulations of cells immunolabeled for 5HT, Som, G, and peptide YY (PYY).
ABSTRACT Among the different cell types present in the respiratory tract of the vertebrates, some... more ABSTRACT Among the different cell types present in the respiratory tract of the vertebrates, some (epithelial, endothelial, neural) specialise in the production of regulatory factors. Endocrine cells occur either single, spread throughout the epithelial lining, or in innervated groups, called 'neuroepithelial bodies' (NEBs). In mammals, these endocrine cells may be involved in lung maturation during perinatal life and in chemoreception. A neuroendocrine diffuse system is present in the respiratory organs of all classes of vertebrates. In amphibians and reptiles, single endocrine cells as well as NEBs are located in the apices of the lung septa. The respiratory tract shows nerve fibres immunoreactive to several neuropeptides. Since some neurons and fibres contain NO synthase a broad evolutionary presence of NO-releasing neurons, probably involved in the control of relaxation, is suggested.
American Journal of Respiratory Cell and Molecular Biology, 1999
Several studies, including histochemical ones, have indicated that nitric oxide (NO) of endotheli... more Several studies, including histochemical ones, have indicated that nitric oxide (NO) of endothelial origin may be related to the pulmonary vasodilation that occurs at birth. Since no histologic studies have been done of the possible parallel perinatal increase in production of neuronal NO synthase (nNOS) by pulmonary nerve plexuses, we investigated the distribution of nNOS in fetal, neonatal, and adult mouse lung. Lungs from mice aged 13 d gestation to 6 d after birth and lungs of adults were studied through histochemistry for nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity and immunocytochemistry. Both techniques gave almost similar results in relation to time of appearance, distribution, and frequency of neural structures positive for NADPH-d and NOS. NADPH-d staining was also applied to whole mounts of developing and adult tracheae. Staining was found from gestational days 13 to 15 onward in a small portion of the neuronal population. In all stages studied, NADPH-d/NOS staining was found in neuron cell bodies in the hilar region and bronchiolar wall, as well as in neuronal processes. Labeled terminal nerve fibers with varicosities were more frequent in pulmonary blood vessels than in airways. In tracheae, similar NADPH-d/NOS-positive nerve plexuses were found. The presence of nNOS in fetal and neonatal mouse respiratory tract suggests that neurally derived NO must play a role in developing lung physiology. However, because no perinatal increase in the number or intensity of staining of nNOS-positive nerve structures was seen, no apparent relation between neural NO and vasodilation can be established at birth.
Journal of Hepatology, Volume 44, Issue null, Pages S198, April 2006, Authors:E. Larrea; JI Riezu... more Journal of Hepatology, Volume 44, Issue null, Pages S198, April 2006, Authors:E. Larrea; JI Riezu-Boj; L. Gil-Guerrero; N. Casares; R. Aldabe; P. Sarobe; MP Civeira; J. Quiroga; L. Guembe; F. Borrás-Cuesta; JJ Lasarte; J. Prieto.
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