A. Van Lommel

The intrapulmonary neuroepithelial bodies after vagotomy: demonstration of their sensory neuroreceptor-like innervation

In the neonatal rabbit, infranodosal vagotomy destroys most of the intracorpuscular nerve endings of the pulmonary neuroepithelial bodies (NEB), while supranodosal vagotomy leaves these nerve endings intact. We conclude that NEB are mainly innervated by sensory neurons whose cell bodies lie in the nodose ganglion of the vagus nerve. These findings support the hypothesis that although secretory in nature, NEB are neuroreceptor structures.

Pulmonary neuroepithelial bodies are innervated by vagal afferent nerves: an investigation with in vivo anterograde DiI tracing and confocal microscopy

Abstract The pulmonary airway and alveolar epithelia contain distinctly innervated clusters of basally granulated cells: the neuroepithelial bodies. In the past, morphological criteria and the results of selective vagotomy have led to the interpretation that their innervation is sensory. Consequently, they are regarded as receptor organs. As a further test of this hypothesis, the present investigation set out to label vagal sensory nerve fibres to the lungs by anterograde neural tracing, and to establish the relationship between these fibres and the neuroepithelial bodies. A fluorescent neural tracer was injected unilaterally into the left or right nodose ganglion of adult rats. After suitable survival times, thick frozen sections of lung tissue were studied with laser scan confocal microscopy. Sensory nerve fibres were seen to run in the airway walls and occasionally penetrated the epithelium, where they formed complex terminals. The resulting intraepithelial sensory end organs showed a close morphological resemblance to the neuroepithelial bodies. Subsequently, electron microscopic investigation of such identified structures revealed the typical ultrastructural characteristics of neuroepithelial bodies: corpuscular cells containing dense cored secretory vesicles and contacted by mitochondria-rich nerve endings. We conclude that anterograde tracing of sensory nerves from the nodose ganglion confirms the receptor nature of the pulmonary neuroepithelial bodies, which may correspond to a subpopulation of the irritant and C-fibre receptors.

Postnatal development of the pulmonary neuroepithelial bodies in various animal species

Various aspects of the postnatal development of intrapulmonary neuroepithelial bodies (NEB) were quantified in guinea-pigs, rabbits, cats, rats and hamsters. The highest densities of NEB were found at birth, especially in species with very immature neonates. Postnatally this density decreased, most probably by lung expansion and growth. The number of corpuscular cells per NEB generally did not change during postnatal development. Likewise, the volume density of their secretory dense cored vesicles remained unchanged. On the other hand, in most species and especially in those with very immature neonates, the number of intracorpuscular NEB nerve endings increased during postnatal development. At the same time, the number of afferent nerve endings increased at the expense of the efferent ones. We argue that NEB serve a dual function: endocrine and chemoreceptor. The endocrine function, dependent on the number of cells and their content of secretory vesicles, is already well developed at birth and does not mature further. The chemoreceptor function, dependent on the innervation, shows considerable maturation in the postnatal period.

Na+/H+ exchange inhibition improves post-transplant myocardial compliance in 4-hour stored donor hearts

Na+/H+ exchange inhibitors have cardioprotective properties. The effects of the new Na+/H+ exchange inhibitor, HOE642 on myocardial function were assessed after transplantation of canine brain-dead and non-brain-dead donor hearts preserved for 4 h. Four groups were studied: brain-dead donors; non-brain-dead donors; brain-dead donors and recipients treated with HOE642 (2 mg/kg); and treated non brain-dead donors and recipients. Donor hearts were stored in NIH2. At the end of 60 min reperfusion after transplantation, pressure-volume curves were constructed. Biopsies were analysed histologically and ultrastructurally. Afterwards, weaning from cardiopulmonary bypass was accomplished. HOE642 improved compliance in hearts from both brain-dead and non-brain-dead donors. No differences in myocardial water content nor in myocardial performance were detected. No irreversible damage was seen ultrastructurally. It is concluded that myocardial compliance after transplantation was improved by administration of HOE642. The use of this inhibitor might improve the current myocardial preservation technique for transplantation.

Sulphated and sulphonated polymers inhibit the initial interaction of hepatitis B virus with hepatocytes

The initial step during hepatitis B virus (HBV) infection is the specific attachment of the virus to the hepatocyte. Here we studied whether the binding of HBV to hepatocytes can, as is the case with most other enveloped viruses, be blocked by polyanionic compounds. Viral particles produced by HepAD38 cells were used as inoculum and HBV-negative HepG2 cells, as well as primary human hepatocytes, as target cells. Three sulphated polymers, that is, PAVAS (a co-polymer of acrylic acid with vinyl alcohol sulphate), heparin and dextran sulphate (DS) (MW 5000), and the sulphonated polymer PAMPS [poly(2-acryl-amido-2-methyl-1-propanesulfonic acid] (MW ≈7000–12000), proved strong inhibitors of the binding of HBV to HepG2 cells and primary hepatocytes. The 50% effective concentration (EC50) for inhibition of HBV binding to HepG2 cells by PAVAS, heparin, DS and PAMPS was 1.3 μg/ml, 1.6 μg/ml, 1.8 μg/ml and 3.3 μg/ml, respectively, and to primary hepatocytes 1.6 μg/ml (PAVAS), 1.6 μg/ml (heparin), 2.6 μg/ml (DS) and 4.1 μg/ml (PAMPS). These values are in the same range as the concentrations required for these compounds to prevent such viruses as herpesviruses and HIV from binding to cells. These findings may be helpful in elucidating the mechanism of the initial interaction of HBV with hepatocytes.

Intimal hyperplasia after long-term venous catheterization.

Objective: Intimal hyperplasia is a well-known consequence of arterial injury and arterialization in vein grafts. However, the subacute and chronic vein wall changes which occur after catheterization have not been well studied. In this animal study, intimal hyperplasia in the vein wall after catheterization was examined. Methods: A silicon catheter was placed in the anterior caval vein of 54 rats. After in situ fixation at scheduled intervals (1 day to 6 months), the pathologic changes in the vein wall were studied on semi-serial histology sections by means of light microscopy. Results: Three forms of intimal hyperplasia could be observed: plaque-like, papillary-like and incorporation of the mural part of the sleeve into the underlying vein wall. Although the appearance of each was different, their composition was identical. All were mainly composed of α-actin-positive cells and collagen localized above the internal elastin layer, and covered by endothelium if facing the lumen. The plaque-like and papillary-like forms were mainly localized in the anterior vena cava, while sleeve incorporation mainly occurred in the jugular vein. Plaque-like and papillary-like intimal hyperplasia could be seen together on the same slide, but these two forms were never seen together with sleeve incorporation. Conclusion: Intimal hyperplasia occurs after venous catheterization and is probably caused by chronic injury to the vein wall due to knocking and rubbing movements of the catheter against the wall.

Pulmonary Neuroepithelial Bodies in Neonatal and Adult Dogs: Histochemistry, Ultrastructure, and Effects of Unilateral Hilar Lung Denervation

In neonatal dogs, neuroepithelial bodies (NEB) are located in the distal lung. They consist of closely packed and granulated epithelial cells showing a positive immune reaction to serotonin and carrying well-developed apical microvilli. They make close contact with capillaries and form morphologically afferent synaptic junctions with intracorpuscular nerve endings. Since most nerve endings degenerate after hilar lung denervation, they are carried by extrinsic, most likely vagal, sensory nerve fibers. We conclude that pulmonary NEB probably are receptor organs, sampling the inspired air and secreting bioactive substances. These might have a local vaso- or bronchoactive regulatory effect, or could be carried to other body parts via the blood vessels. In addition, NEB might induce integrative reflexes via the central nervous system.The NEB intracorpuscular nerve endings also show spontaneous degeneration. This, in addition to the scarcity of NEB in the distal lungs of adult dogs, strongly suggests that the pulmonary NEB are particularly important during the perinatal period of life.

Immunocytochemical localization of a diuretic hormone of the beetle Tenebrio molitor, Tenmo-DH(37), in nervous system and midgut.

Abstract. Although the mealworm Tenebrio molitor inhabits very dry environments, it has at least two diuretic peptides, which increase fluid secretion by the free portions of the Malpighian tubules. Unlike other insect corticotropin-releasing factor (CRF)-related peptides isolated to date, these are non-amidated peptides. The immunocytochemical localization of Tenmo-DH37 was investigated using antisera raised against this hormone. Immunoreactive neurosecretory cells were found in the brain and abdominal ganglia with immunoreactive processes projecting to the peripheral nervous system. Intense staining of the neurohaemal release site, the corpora cardiaca, was observed. In addition, neurosecretory cells immunoreactive to Tenmo-DH37 were found in the posterior midgut and a network of immunoreactive nerve processes extended over the surface of the midgut. Tenmo-DH37 is widely distributed and its staining pattern resembles that found for other, amidated CRF-related diuretic peptides.

ASSOCIATION OF IMMUNE CELLS WITH NEUROEPITHELIAL BODIES IN THE LUNGS OF NEONATAL DOGS, CATS AND HAMSTERS

A close topographical association between neuroepithelial bodies and immune cells is occasionally observed in the lungs of various neonatal mammalian species. The immune cells concerned are mast cells and neutrophil or eosinophil granulocytes. In the lungs of newborn puppies having undergone left lung autotransplantation, mast cells are particularly numerous in the airway mucosa of both right and left lungs and their association with neuroepithelial bodies is highly significant. Several of the substances known to be synthesized by the neuroepithelial bodies have a chemoattractive effect on immune cells. Thus, our observations indicate that intrapulmonary neuroepithelial bodies contribute to the local immune response.

Neuroepithelial Bodies in Relatively Mature Lungs: An Investigation in Prenatal and Newborn Lambs

Lungs of fetal and neonatal lambs were found to contain small, inconspicuous and widely dispersed neuroepithelial bodies (NEB). Under the light microscope, NEB could only be identified with certainty by their positive immune reaction to antibodies against serotonin. At the ultrastructural level, a large number of dense-cored vesicles was found in the corpuscular cells of the NEB. However, the number of intracorpuscular nerve endings was small. We conclude from these findings that, in the lamb, NEB act primarily as local regulators of lung function and that their reflex-mediated actions may be of secondary importance. This may be related to the fact that lungs of lambs at birth are relatively mature compared to those of various other species. Increased maturation of lungs and a concomitant decreased risk of insufficient oxygenation might be associated with the presence of an oxygen-sensitive chemoreceptor with primarily local actions for prevention of hypoxia.