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F Sundler

Publications and source records attributed to F Sundler.

At least 91 records · Page 5Linked to original sources
PubMed1997

Allergic eosinophil-rich inflammation develops in lungs and airways of B cell-deficient mice.

Immunoglobulins (Ig), particularly IgE, are believed to be crucially involved in the pathogenesis of asthma and, equally, in allergic models of the disease. To validate this paradigm we examined homozygous mutant C57BL/6 mice, which are B cell deficient, lacking all Ig. Mice were immunized intraperitoneally with 10 micrograms ovalbumin (OVA) plus alum, followed by daily (day 14-20) 30 min exposures to OVA aerosol (OVA/OVA group). Three control groups were run: OVA intraperitoneally plus saline (SAL) aerosol (OVA/SAL group); saline intraperitoneally plus saline aerosol; saline intraperitoneally plus OVA aerosol (n = 6-7). Lung and large airway tissues obtained 24 h after the last OVA or SAL exposure were examined by light microscopy and transmission electron microscopy (TEM). The Ig-deficient mice receiving OVA/ OVA treatment had swollen and discolored lungs and exhibited marked eosinophilia both in large airway subepithelial tissue (49.2 +/- 12.0 cells/mm basement membrane [BM] versus OVA/ SAL control 1.2 +/- 0.3 cells/mm BM; P < 0.001), and perivascularly and peribronchially in the lung (49.3 +/- 9.0 cells/unit area versus OVA/SAL control 2.6 +/- 0.6 cells/unit area; P < 0.001). The eosinophilia extended to the regional lymph nodes. TEM confirmed the subepithelial and perivascular localization of eosinophils. Mucus cells in large airway epithelium increased from 1.5 +/- 0.8 (OVA/SAL mice) to 39.5 +/- 5.7 cells/mm BM in OVA/OVA treated mice (P < 0.001). OVA/SAL mice never differed from the other control groups. Corresponding experiments in wild-type mice (n = 6-7 in each group) showed qualitatively similar but less pronounced eosinophil and mucus cell changes. Macrophages and CD4+ T cells increased in lungs of all OVA/OVA-treated mice. Mast cell number did not differ but degranulation was detected only in OVA/OVA-treated wild-type mice. Immunization to OVA followed by OVA challenges thus cause eosinophil-rich inflammation in airways and lungs of mice without involvement of B cells and Ig.

Animals↗
PubMed1997

Developmental expression of NPY, PYY and PP in the rat pancreas and their coexistence with islet hormones.

It has been suggested that members of the neuropeptide Y (NPY) family of regulatory peptides [NPY, peptide YY (PYY) and pancreatic polypeptide (PP)] play an important role in the development of the endocrine pancreas. The development of rat endocrine pancreas from embryonic (E) day 12 until 30 days postpartum (P) was studied with emphasis on NPY, PYY and PP and their co-existence with insulin, glucagon and somatostatin using single and double immunostaining and in situ hybridization. Already at E12, PYY was detectable in small endocrine cell clusters and found to be co-localised with both insulin and glucagon, which at this stage occurred in the same cells. At E16 most of the insulin-immunoreactive (IR) cells were distinct from the glucagon/PYY-IR cells. Interestingly, at E16 NPY mRNA, and at E17 NPY immunoreactivity appeared in a few, scattered endocrine cells. Virtually all NPY-IR endocrine cells were insulin-producing beta cells. At E18 the endocrine cells started to form typical islets with centrally located insulin/NPY-IR cells surrounded by glucagon/PYY-IR cells. AT E20-E21, the vast majority of insulin-producing cells also expressed NPY. However, at birth (day 0) islet cell NPY mRNA was lacking. Postnatally the number and immunostaining intensity of NPY-IR islet cells rapidly declined, being non-detectable at P5. Cells containing PP immunoreactivity and PP mRNA were first detected at E21. The adult pattern of islet peptide distribution, with NPY confined to neuronal elements. PYY and PP exclusively in endocrine cells, was established at P5. The beta cell expression of NPY during the latter part of embryogenesis coincides with the prepartal glucocorticoid surge and with rapid islet cell replication and differentiation. This is compatible with steroid induction of NPY expression and with a role for NPY in the maturation of beta cells and their hormone release, which occurs in the immediate neonatal period.

Animals↗
PubMed1997

Parathyroid function and histology in patients with parathyroid adenoma: correlation of clinical and morphologic findings.

Serum levels of parathyroid hormone (PTH), alkaline phosphatase (ALP), calcium, creatinine, and vitamin D and the glomerular filtration rate were compared with the histologic properties and expression of PTH and chromogranin A in excised parathyroid adenomas from patients with primary hyperparathyroidism (pHPT). PTH and chromogranin A were detected immunohistochemically, and their mRNA was demonstrated by in situ hybridization with quantification of their mRNA levels by image analysis. There was a positive correlation between the cellular levels of PTH mRNA and the cellular levels of chromogranin A mRNA (r = 4.4; p < 0.05). However, within certain parts of the adenomas, mostly consisting of chief cells, the expression of PTH mRNA and chromogranin A mRNA was heterogeneous and the levels did not correspond to each other. A reduced suppressibility of PTH in patients with pHPT was confirmed. Although cellular levels of PTH and chromogranin A and their mRNAs were low in the oxyphilic parts of the adenomas, there was no correlation between the amount of oxyphilic cells in the adenomas and the suppressibility of PTH by calcium. There was also no association between the cellular levels of PTH mRNA or chromogranin A mRNA as studied by image analysis and "calcium sensitivity." Our results thus demonstrate that although PTH and chromogranin A mRNA levels are in general correlated to each other there are differences in their expression within and between individual parathyroid adenomas. It therefore seems likely that the expression of PTH and chromogranin A are differentially regulated, and that PTH and chromogranin A may not always be co-secreted. This point could be of importance, as chromogranin A and its cleavage products are known to influence PTH secretion.

Adenoma↗
PubMed1997

Developmental expression of neuronal and endocrine markers in the parathyroid glands of the rat.

The parathyroid glands of the adult rat harbor a number of neuroendocrine markers, biologically active peptides and "classical" neuromessengers in addition to parathyroid hormone (PTH). Their appearance during parathyroid development is, however, not known. In the present study we have examined several neuroendocrine markers and neuromessengers in the parathyroid glands of the developing rat [embryonic stage 21(E21), newborn, 1, 2, 3, 4 week old, and adult rats] using immunocytochemistry. Chromogranin A- and PTH-mRNA were also examined by in situ hybridization and the mRNA levels were quantitated by computerized image analysis. Protein gene product 9.5- and synaptophysin-containing nerve fibers appeared already before birth and then gradually increased in number postnatally, and at the age of 4 weeks the nerve fibers were moderate in number to numerous. Nerve fibers containing calcitonin gene-related peptide, neuropeptide Y and vasoactive intestinal polypeptide also increased gradually in number, while galanin-, substance P- and tyrosine hydroxylase-containing fibers remained few throughout development. The glandular cells expressed chromogranin A, pancreastatin and PTH already before birth. The levels of chromogranin A- and PTH-mRNA were low at E21 and increased markedly at birth; chromogranin A mRNA levels had increased even more at 1 week postnatally. Three to 4 weeks after birth the levels of PTH- and chromogranin A mRNA again increased, then stabilized at a slightly lower level in the adult rat. Our findings demonstrate that the parathyroid glands of rat are already innervated and express PTH and chromogranin A before birth and that the density of peptide-containing nerve fibers changes during development. The stepwise increases of PTH- and chromogranin A mRNAs during development indicate marked changes in parathyroid activity occurring at birth and at weaning.

Age Factors↗
PubMed1997

Dissociated insulinotropic sensitivity to glucose and carbachol in high-fat diet-induced insulin resistance in C57BL/6J mice.

To study islet function following reduced insulin sensitivity, we examined mice of the C57BL/6J strain, the genotype of which carries an increased propensity to develop insulin resistance when metabolically challenged. The mice received either a high-fat diet (58% fat on an energy basis) or a control diet (11% fat) for 12 weeks. The body weight of mice on the high-fat diet increased significantly more than that of mice on the control diet (25.8 +/- 0.4 v 21.3 +/- 0.2 g, P < .001). Already after 1 week on the high-fat diet, a significant hyperglycemia accompanied by hyperinsulinemia had evolved, indicative of insulin resistance. After 12 weeks, plasma glucose levels for high-fat diet-treated mice were 7.5 +/- 0.1 mmol/L, versus 6.5 +/- 0.1 mmol/L in controls (P < .001); corresponding values for plasma insulin were 248 +/- 17 and 104 +/- 7 pmol/L, respectively (P < .001). Mice given a high-fat diet also had elevated levels of total cholesterol, triglycerides, and free fatty acids (FFAs) compared with controls. After 4, 8, and 12 weeks, glucose (2.8, 8.3, or 16.7 mmol/kg) or the cholinergic agonist carbachol (0.16 or 0.53 micromol/kg) was injected intraperitoneally. The insulinotropic response to glucose was not different between the two groups after 4 or 8 weeks, whereas after 12 weeks, glucose-induced insulin secretion was markedly impaired in high-fat diet-treated mice (P < .001). In contrast, after 8 and 12 weeks on a high-fat diet, carbachol-stimulated insulin secretion was potentiated (P < .01), whereas carbachol-stimulated glucagon secretion was not significantly altered. Furthermore, after 12 weeks on the high-fat diet, insulin secretion from isolated islets was impaired at glucose levels of 8.3, 11.1, and 16.7 mmol/L (P < or = .05). Moreover, islet morphology as examined by immunocytochemistry using insulin antibodies and islet innervation, as revealed by immunostaining of tyrosine hydroxylase (TH), neuropeptide Y (NPY), galanin, vasoactive intestinal polypeptide (VIP), and substance P (SP) were unaffected by the high-fat diet for 12 weeks. However, quantitative in situ hybridization showed a 3.5-fold upregulation of insulin gene expression in response to the high-fat diet (P < .001) despite unaltered B-cell mass and pancreatic insulin content. We conclude that as little as 1 week of treatment with a high-fat diet induces insulin resistance in C57BL/6J mice. This is accompanied later by hyperlipemia, potentiated carbachol-stimulated insulin secretion, and increased insulin gene expression but impaired glucose-stimulated insulin secretion. We suggest that after several weeks' duration, insulin resistance is accompanied by enhanced islet sensitivity to cholinergic activation and exaggerated insulin gene expression, whereas the failing islet sensitivity to glucose represents decompensation.

Animals↗
PubMed1997

The mouse trap.

Mouse models of asthma are now being used extensively in drug research. However, the successful unravelling of combinatorial interplays of cells and molecules in the murine airways may not be matched by equally successful demonstrations of an asthma-like pathophysiology. Here, Carl Persson, Jonas Erjefält, Magnus Korsgren and Frank Sundler discuss the fact that major features of asthma may still need to be demonstrated in the airways of allergic mice.

Allergens↗
PubMed1997

Islet amyloid polypeptide and calcitonin gene-related peptide expression are down-regulated in dorsal root ganglia upon sciatic nerve transection.

Islet amyloid polypeptide (IAPP) is structurally related to calcitonin gene-related peptide (CGRP) and has been implicated in glucose homeostasis and diabetes pathogenesis because it is expressed in insulin cells and forms amyloid in pancreatic islets from type II diabetic patients. IAPP is also constitutively co-expressed with CGRP in rat sensory neurons. Whether expression of IAPP is altered by nerve injury with or without regeneration was investigated in adult rats subjected to unilateral sciatic axotomy; IAPP and CGRP expression were determined by quantitative in situ hybridization and immunocytochemistry at days 3, 10 and 30 after axotomy. In ipsilateral L4-L5 dorsal root ganglia (DRG), the percentages of nerve cell profiles labelled for IAPP and CGRP mRNA were reduced at all time points studied. IAPP and CGRP mRNA expression were lower in nerve cell profiles in ipsilateral DRGs compared to the contralateral side after axotomy alone whereas epineurial nerve suture maintained or restored IAPP and CGRP expression. The numbers of IAPP- and CGRP-immunoreactive DRG nerve cell profiles and dorsal horn fibers were reduced on the ipsilateral side at all time points. Thus, IAPP and CGRP expression are down-regulated upon axotomy. Nerve repair maintains or restores IAPP and CGRP expression in individual neurons but does not prevent the loss of CGRP/IAPP phenotype of some of these neurons in response to axotomy.

Amyloid↗
PubMed1997

Islet amyloid polypeptide in the gut and pancreas: localization, ontogeny and gut motility effects.

The occurrence of islet amyloid polypeptide (IAPP) in the gut and pancreas of several species and during ontogeny of the rat, was studied using immunocytochemistry. Effects of IAPP on rat ileal smooth muscle were assessed in vitro. Islets of most, but not all, species examined, displayed IAPP in insulin cells and, in some species, also in somatostatin- and peptide YY (PYY)-containing cells. In the gut, expression of IAPP varied among species; when present, IAPP was most abundant in the proximal part and co-localized with somatostatin, PYY, gastrin/cholecystokinin, enteroglucagon or serotonin. IAPP was first demonstrated at embryonic day 12 and 16 in islet and gastrointestinal endocrine cells, respectively. IAPP relaxed gut muscle and reduced electrical field stimulation-evoked contractions, presumably by inhibiting acetylcholine release. Thus, IAPP expression in islets is consistent with an important role for IAPP in fuel metabolism; the gastrointestinal expression and motor effects of IAPP suggest that IAPP may modulate gastrointestinal function.

Amyloid↗
PubMed1997

Effects of topical platelet activating factor on the guinea-pig tracheobronchial mucosa in vivo.

Platelet activating factor (PAF) has been reported to produce a variety of airway effects including epithelial damage and increased airway-lung absorption of hydrophilic tracers. The present study examines effects of PAF on the guinea-pig tracheobronchial mucosa in vivo. Vehicle with and without PAF (4.0 and 8.0 nmol) was superfused onto the tracheobronchial mucosa. The levels of 125I-albumin, previously given intravenously, were determined in tracheobronchial lavage fluids as an index of mucosal exudation of plasma. The mucosa was also examined by scanning electron microscopy. In separate animals, 99mTc-DTPA (a low molecular weight, 492 Da, hydrophilic tracer) was superfused onto the mucosal surface through an oro-tracheal catheter, together with vehicle or PAF (8.0 nmol). A gamma camera determined the disappearance rate of 99mTc-DTPA from the airways as an index of mucosal absorption. PAF produced dose-dependent mucosal exudation of plasma up to 20-fold greater than control (P < 0.001). However, PAF did not damage the epithelium and the absorption ability of the airway mucosa was unaffected. The results, in contrast to previous reports, suggest that PAF may not readily damage the airway mucosa even at large exudative doses of the agent. The present finding support the view that the plasticity of the epithelial junctions allows the creation of valve-like paracellular pathways for unidirectional clearance of extravasated plasma into the airway lumen. We suggest that endogenous PAF may participate in first line respiratory defence reactions by causing lumenal entry of bulk plasma without harming the epithelium.

Administration, Topical↗
PubMed1997

Prompt epithelial damage and restitution processes in allergen challenged guinea-pig trachea in vivo.

BACKGROUND: Little is known about the induction and the morphology of epithelial damage, and of the ensuing epithelial restitution processes in allergic airways. OBJECTIVE: To examine epithelial damage and restitution in allergen challenged guinea-pig trachea. METHODS: Whole-mount techniques, transmission and scanning electron microscopy, cryosectioning, and histochemical staining were used. Cell proliferation was monitored by BrdU-immunohistochemistry. RESULTS: Allergen challenge produced patchy, crater-like, and leucocyte-rich epithelial damage sites. At 1, 5, and 24 h damage was associated with poorly differentiated epithelial restitution cells. Already at 1 h the epithelial craters had a floor of flattened restitution cells and the damaged areas comprised < 1% of the mucosal surface area (whole-mount preparations). In contrast, cryo sections displayed large areas (approximately 20%, 1 h) of denudation. Epithelial, and subepithelial (fibroblasts, smooth muscle) proliferation was increased 5 and 24 h after challenge (P < 0.01). CONCLUSION: Within 1 h allergen challenge has induced patchy damage sites where epithelial restitution is already advanced; although easily produced by cryosectioning frank denudation was not evident in whole-mount preparations. The present findings may explain the well maintained, functional tightness of allergic airways displaying epithelial damage, shedding, and even denudation. The present data also suggest the possibility that epithelial damage-restitution may be causative to allergic airway remodelling.

Allergens↗
PubMed1997

Neuropeptides in idiopathic chronic constipation (slow transit constipation).

Tissue specimens from the large bowel of 18 patients with long-standing slow transit constipation were investigated to determine the distribution and density of several neuropeptides and amines in the enteric nerve system, and also of endocrine cells in comparison to normal individuals. CGRP (calcitonin gene-related peptide), galanin, glucagon, GRP (gastrin-releasing peptide), metenkephalin, motilin, neuropeptide Y (NPY), PACAP, peptide YY (PYY), serotonin, somatostatin, substance P and VIP were studied by immunohistochemistry. Tissue concentrations of VIP, substance P and galanin were also measured by radioimmunoassay. Significantly increased VIP, SP and galanin contents were found in specimens from the ascending colon. Levels of VIP and galanin were also increased in the transverse colon. Immunohistochemistry revealed only marginal changes with an increased density of PACAP nerve fibres in the smooth muscle and of VIP and PACAP nerves in the myenteric plexus of the transverse colon. In the descending colon substance P and NPY immunoreactivity were also increased in the myenteric plexus while the density of VIP nerve fibres was reduced in the mucosa/submucosa. The frequency of PYY-containing cells and the 5-HT-containing cells in the ascending colon was significantly increased in the constipated patients.

Adult↗
PubMed1997

Pituitary adenylate cyclase activating polypeptide and nitric oxide synthase are expressed in the rat ciliary ganglion.

AIMS: To study the distribution in the rat ciliary ganglion of neurons synthesising and storing the recently discovered neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) and neuronal nitric oxide synthase (NOS), the neuronal marker of the novel gaseous transmitter nitric oxide. METHODS: Neurons expressing PACAP and neuronal NOS mRNA were identified in the rat ciliary ganglion by in situ hybridisation with radiolabelled oligonucleotide probes. Immunocytochemistry was used to demonstrate immunoreactive neuropeptides and NOS. RESULTS: Immunocytochemistry demonstrated immunoreactivity for PACAP and NOS in a small number of neuronal cell bodies. In situ hybridisation revealed that NOS and PACAP were expressed in numerous ganglion cell somata. The well established ciliary messengers vasoactive intestinal peptide and neuropeptide Y were found in a large number of neuronal cell bodies. CONCLUSION: These results demonstrate that PACAP and NOS are synthesised and stored in the ciliary ganglion. These findings further illustrate the mixed nature of the ciliary ganglion and may provide a basis for the understanding of the diverse physiological functions of this ganglion.

Animals↗
PubMed1997

Epithelial barrier formation by airway basal cells.

BACKGROUND: Epithelial shedding processes in airway inflammation and defence may produce damaged areas where basal cells are the main remaining epithelial cell type. The present study examines the capacity of basal cells to form an epithelial barrier structure after loss of columnar epithelial cells. METHODS: A technique was developed which allows selective removal of columnar epithelial cells from isolated airways. A drop of tissue adhesive glue was applied on the mucosal surface shortly after excision of guinea pig trachea and human bronchus. Gentle removal of the glue, together with attached columnar cells, left a single layer of cobbled, solitary basal cells. The tissue was kept in culture media. Morphological changes of the basal cells were monitored by immuno-histochemistry and scanning and transmission electron microscopy at several time points. RESULTS: After 20 minutes the basal cells had undergone extensive flattening and established contact with each other. The basement membrane thus became covered by a poorly differentiated epithelium in both guinea pig and human airways. Abundant interdigitating cytoplasmic protrusions were observed at cell borders. CONCLUSIONS: Basal cells promptly flatten out to cover the basement membrane at loss of neighbouring columnar cells. These data may explain why the epithelial barrier function may be uncompromised in desquamative airway diseases. Furthermore, they suggest the possibility that sacrificial release of columnar epithelial cells and prompt creation of a barrier structure constitute important roles of basal cells in airway defence against severe insults.

Animals↗
PubMed1997

Presynaptic sympathetic mechanism in the insulinostatic effect of epinephrine in mouse pancreatic islets.

The catecholamines inhibit insulin release. It is not established whether presynaptic mechanisms contribute to this effect. We therefore examined the relative contribution of presynaptic and postsynaptic mechanisms to the insulinostatic effects of epinephrine and norepinephrine. Mice were injected with 6-hydroxydopamine (6-OHDA; 0.19 mmol/kg) or its vehicle. Islets were isolated after 48 h. Islets from vehicle-injected control animals contained numerous tyrosine hydroxylase (TH)-immunoreactive nerve terminals (marker for sympathetic nerves). In contrast, TH-immunoreactive nerves were not detected in islets from 6-OHDA-treated animals, indicating sympathetic denervation. Basal (5.6 mmol/l glucose) or glucose-stimulated (16.7 mmol/l) insulin secretion did not differ between incubated islets from vehicle-injected control animals and islets from 6-OHDA-treated animals. The insulinostatic effect of epinephrine, but not that of norepinephrine, was markedly impaired in islets from 6-OHDA-treated animals: the lowest effective insulinostatic concentration of epinephrine was 0.01 nmol/l in islets from vehicle-injected animals and 1 nmol/l in islets from 6-OHDA-treated animals. We conclude that in isolated mouse islets the insulinostatic effect of epinephrine, but not that of norepinephrine, partially depends on sympathetic nerve terminals, suggesting an important role for presynaptic mechanisms in epinephrine-induced inhibition of insulin secretion.

Animals↗
PubMed1997

Differential effect of insulin treatment on islet amyloid polypeptide (amylin) and insulin gene expression in streptozotocin-induced diabetes in rats.

Islet amyloid polypeptide (IAPP) is a beta cell hormone, which forms islet amyloid in non-insulin-dependent diabetes mellitus and may oppose insulin action and release. Therefore, the previously observed relative overexpression of IAPP compared with insulin in streptozotocin-treated rats could be unfavourable if it occurs in diabetes. Using quantitative in situ hybridization, we examined whether insulin treatment affected IAPP and insulin gene expression and their ratio at day 8 and 20 after induction of streptozotocin diabetes (plasma glucose approximately 30 mM). Total islet IAPP mRNA levels were less reduced than those of insulin at both time points. Differential regulation of the two hormones was further reflected by mean IAPP mRNA levels in the remaining islet cells being unaffected by streptozotocin treatment, whereas those of insulin were reduced. At both time points, insulin treatment decreased total islet levels of IAPP and insulin mRNA even more, IAPP mRNA levels being less reduced. Mean insulin mRNA levels, but not IAPP mRNA levels, in the remaining islet cells were reduced by insulin treatment. Between time points, total islet mRNA levels were higher at day 20, while mean mRNA levels in the remaining islet cells were unchanged, suggesting that regeneration of beta cells had occurred. In contrast, insulin gene expression was the same at both time points in insulin-treated rats, suggesting that insulin impaired insulin expression. To summarize, we found that IAPP and insulin were differentially expressed in experimental diabetes and that insulin treatment inhibited insulin, but not IAPP, gene expression. It is therefore unlikely that insulin will protect against amyloid formation and metabolic perturbations which may arise as a consequence of IAPP overexpression.

Amyloid↗
PubMed1997

Motor responses in rat ileum evoked by nitric oxide donors vs. field stimulation: modulation by pituitary adenylate cyclase-activating peptide, forskolin and guanylate cyclase inhibitors.

This study examines nitric oxide (NO) mediated effects on longitudinal muscle with adherent myenteric ganglia from rat ileum in vitro using NO donors and electrical field stimulation. Electrical field stimulation (20 Hz) caused a biphasic response-a relaxation followed by a contraction. NG-nitro-L-arginine methyl ester almost totally abolished the relaxation and L-arginine restored it. The contraction was unaffected. The NO donors sodium-nitroso-N-acetylpenicillamine (SNAP) and sodium-nitroprusside also induced a biphasic response, a contraction followed by relaxation. Relaxations mediated by neuronally released NO were not blocked by methylene blue or 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one suggesting that they are independent of a rise in intracellular cyclic guanylate cyclase. Their amplitude was unaffected by forskolin. The relaxations evoked by NO (or a NO-related substance) liberated from SNAP were blocked by methylene blue or 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one indicating a cyclic guanylate cyclase-dependent mechanism of action. Pituitary adenylate cyclase-activating peptide and forskolin, but not vasoactive intestinal peptide or neuropeptide Y, caused a marked leftward shift of the concentration-response curve of the SNAP-induced relaxation. The contractions induced by SNAP were blocked by methylene blue and 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one and thus, cyclic guanylate cyclase dependent. The SNAP-induced contractions were abolished by pituitary adenylate cyclase-activating peptide and forskolin, but unaffected by vasoactive intestinal peptide or NPY. In conclusion, motor responses evoked by NO released from NO donors vs. neuronally released NO reveals different mechanisms of action.

Animals↗
PubMed1997

Association between inflammation and epithelial damage-restitution processes in allergic airways in vivo.

BACKGROUND: Associations between allergen challenge-induced sites of epithelial damage and the distribution of leucocytes and extravasated plasma remain unexplored. OBJECTIVE: To study neutrophils, eosinophils, and fibrinogen at allergen challenge-induced patchy epithelial damage-restitution sites in guinea-pig trachea. METHODS: After local challenge tracheal tissue (cryo sections and whole-mounts) and lumen (selective tracheal lavage) were examined at 1, 5, and 24 h. Eosinophils, neutrophils and fibrinogen were identified by histochemistry. RESULTS: Neutrophils increased markedly in tracheal lavage fluids and in tissue and were strongly associated with the challenge-induced epithelial craters of damage-restitution. At 1 and 24 h eosinophils were increased in the tracheal lumen whereas the surrounding tissue displayed a reversed pattern. Gels rich in fibrinogen, neutrophils, and eosinophils were present in epithelial crater areas, protruding into the lumen. Clusters of free eosinophil granules, Cfegs, released through lysis of eosinophils, and neutrophils with long cytoplasmatic protrusions abounded in these crater areas. CONCLUSION: The present findings provide important new insights into allergic airways where sites of epithelial damage-restitution processes emerge as the major loci for eosinophil, neutrophil, and plasma protein activities, the latter likely causing leukocyte adhesion and activation in vivo. The distribution of eosinophils in this study suggests roles of these cells both in airway mucosa and in regional lymph nodes. Based on the present study we also propose that lysis of eosinophils and Cfegs generation are a major paradigm for activation of these cells in vivo.

Allergens↗