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Conditionally immortal neuroepithelial stem cell grafts restore spatial learning in rats with lesions at the source of cholinergic forebrain projections cholinergic forebrain projections Conditionally immortal neuroepithelial stem cell grafts restore spatial leaming in rats with lesions at the source of cholinergic forebrain projections.

Purpose: Loss of cholinergic projections from the basal forebrain (BF) to the cortex and from the medial septal area (MSA) to tbe hippocampus is a reliable correlate of cognitive deficits in aging and Alzheimer's disease (AD). We assessed the capacity of grafts of the conditionally immortal MHP36 clonal stem cell line to improve spatial learning in rats showing profound deficits after lesions to these projections. Methods: Rats were lesioned by infusions of S-AMPA unilaterally into BF or bilaterally into both BF and MSA. MHP36 cells were implanted ipsilaterally in cortex or basal forebrain two weeks after unilateral BF lesions, and in cortex and hippocampus bilaterally six months after bilateral BF-MSA lesions. Intact and lesion-only controls received vehicle. Six weeks later rats were assessed in spatial learning and memory tasks in the water maze, and then perfused for identification of grafted cells by beta-galactosidase immunohistocheniistry. Results: Lesioned rats with MHP36 grafts, whether implanted two weeks or six months after lesioning, learned to find a submerged platform in the water maze as rapidly as intact controls, and showed a strong preference for the platform quadrant on probe trials, whereas lesioned controls were impaired in all measures. Grafted cells of both neuronal and glial morphologies, migrated away from cortical implantation sites in BF Lesioned rats to the striatum, thalamus and basal forebrain lesion area. Cells implanted in basal forebrain showed a similar distribution. In rats with bilateral BF-MSA lesions, grafts implanted in the hippocampus migrated widely through all layers but cortical grafts largely escaped up the needle tract into the meninges. Conclusions: Although MHP36 grafts were functionally effective in both lesion models, the site and age of lesions and site of implantation influenced the pattern of engraftment. This flexibility encourages the development of conditionally immortal human stem cell lines with similar capacities for functional repair of variable neuronal degeneration in AD or aging.

Journal Article↗

Structure of the respiratory tract of the red-bellied newt Cynops pyrrhogaster, with reference to serotonin-positive neuroepithelial endocrine cells.

To investigate the distribution of serotonin-positive neuroepithelial endocrine (NEE) cells in the respiratory tract of the red-bellied newt Cynops pyrrhogaster, serial sections of the respiratory tract were stained using immunohistochemical methods for serotonin, a periodic acid-Schiff method and hematoxylin-eosin staining. The respiratory tract of the red-bellied newt consisted of a tubular laryngotrachea and two pulmonary sacs. Serotonin-positive solitary NEE cells were distributed widely throughout the ciliomucous epithelium of the laryngotrachea. The innervated clusters of NEE cells, termed neuroepithelial bodies, were rarely found in the caudal portion of the laryngotrachea. The density of NEE cells was high in the middle portion of the laryngotrachea, particularly in the region surrounded by a striated laryngeal sphincter, and the densities were low cranially towards the aditus laryngis and caudally in the pulmonary sacs, the epithelium of which consisted of both ciliomucous epithelial cells and non-ciliated respiratory epithelial cells or pneumocytes. The NEE cells were not observed in the vicinity of non-ciliated respiratory epithelial cells. The morphology and distribution of serotonin-positive NEE cells in the respiratory tract of the red-bellied newt were similar to those described in mammals, including humans. The close localization of NEE cells with ciliary and mucous cells and the distribution of NEE cells in the laryngotrachea suggest that NEE cells play important roles in the defense and repair of the ciliomucous epithelium, such as increasing mucous secretion, ciliary beat frequency and the proliferation of epithelial cells.

Animals↗

Control by the extracellular environment of differentiation pathways in 1003 embryonal carcinoma cells: study at the level of specific intermediate filaments.

1003 is a multipotential embryonal carcinoma (EC) clonal cell line which can be induced to follow different developmental pathways by altering the composition of the culture medium. When grown in serum-containing medium the great majority of 1003 cells remain undifferentiated; they express the ECMA 7 cell-surface embryonic antigen and very low amounts of vimentin. In serum-free medium, most 1003 cells differentiate into neuroepithelial cells. The majority of these cells are still labelled with ECMA 7 antibodies. They contain higher amounts of vimentin than EC cells, but no neurofilament proteins. Neuroepithelial cells then differentiate into neurons through a stage of preneurons containing both vimentin and the 70-K neurofilament protein. Fully differentiated neurons contain 70-K neurofilament protein but no vimentin. The 200-K neurofilament protein is detected later in the neurons. Mesenchymal cells (induced by re-adding serum) express high amounts of vimentin organized in networks. Preneurons , neurons, and mesenchymal cells do not express ECMA 7 antigen.

Animals↗

Human cytomegalovirus causes productive infection and neuronal injury in differentiating fetal human central nervous system neuroepithelial precursor cells.

OBJECTIVES: To study the effect of cell differentiation on the vulnerability of human neural cell types to human cytomegalovirus (HCMV) infection. STUDY DESIGN/METHODS: Primary cultures of human fetal neuroepithelial stem cells and differentiating neuroepithelial precursor cells were infected with HCMV strain AD169. Infectious virus production, apoptosis, and viral-associated cytopathic effects then were examined over a 5-day period. RESULTS: HCMV established productive infection in these cells, generating 10-fold amplification of infectious virus. There was no significant difference in the percentage of apoptotic cells in HCMV-infected versus mock-infected cultures. HCMV antigen and specific cytopathic effects were observed in differentiating astrocytes and neurons, although HCMV antigen was 2-fold more frequent among postmitotic neurons. CONCLUSIONS: Neuroepithelial precursor cells and differentiating astrocytes and neurons are permissive to cytopathic HCMV infection, suggesting that the fetal human central nervous system is vulnerable to HCMV-induced neuronal injury at its earliest stages of development.

Apoptosis↗

Expression of EGF receptor and FGF receptor isoforms during neuroepithelial stem cell differentiation.

To characterize the role of epidermal growth factor (EGF) and fibroblast growth factor (FGF) in regulating neuroepithelial stem cells differentiation, we have examined the expression of FGF, EGF, and their receptors by neuroepithelial (NEP) cells and their derivatives. Our results indicate that undifferentiated NEP cells express a subset of FGF receptor (FGFR) isoforms, but do not express platelet-derived growth factor receptors (PDGFRs) or epidermal growth factor receptor (EGFR). The FGFR pattern of expression by differentiated neuron and glial cells differs from that found on NEP stem cells. FGFR-4 is uniquely expressed on NEP cells, while FGFR-1 is expressed by both NEP cells and neurons, and FGFR-2 is down-regulated during neuronal differentiation. FGFRs present on astrocytes and oligodendrocytes also represent a subset of those present on NEP cells. Expression of FGF and EGF by NEP cells and their progeny was also examined. NEP cells synthesize detectable levels of both FGF-1 and FGF-2, and EGF. FGF-1 and FGF-2 synthesis is likely to be biologically relevant, as cells grown at high density do not require exogenous FGF for their survival and cells grown in the presence of neutralizing antibodies to FGF show a reduction in cell survival and division. Thus, neuroepithelial cells synthesize and respond to FGF, but not to EGF, and are therefore distinct from other neural stem cells (neurospheres). The unique pattern of expression of FGF isoforms may serve to distinguish NEP cells from their more differentiated progeny.

Animals↗

Isolation and characterization of putative O2 chemoreceptor cells from the gills of channel catfish (Ictalurus punctatus).

Little is known about the cells or mechanisms of O2 chemoreception in vertebrates other than mammals. The purpose of this study, therefore, was to identify O2-sensitive chemoreceptors in a fish. Putative O2-sensitive chemoreceptors were dissociated from the gills of channel catfish, Ictalurus punctatus, and cultured. A population of cells was identified with morphology and a histochemical profile similar to mammalian carotid body Type I (glomus) cells and pulmonary neuroepithelial cells. These cells stain with neutral red and appear to be the branchial neuroepithelial cells. Immunocytochemical staining showed that these cells contain neuron-specific enolase (NSE), tyrosine hydroxylase (TH) and 5-hydroxytryptamine (5HT). Patch-clamp experiments showed that these cells have a O2-sensitive, voltage-dependent outward K+ current like mammalian O2 sensors. Two kinds of electrophysiological responses to hypoxia (P(O2) < 10 Torr) were observed. Some cells showed inhibition of outward current in response to hypoxia, whereas other cells showed potentiation. Neurochemical content and electrophysiological responses to hypoxia indicate that these cells are piscine O2-sensitive chemoreceptors.

Animals↗

Basic fibroblast growth factor endows dorsal telencephalic neural progenitors with the ability to differentiate into oligodendrocytes but not gamma-aminobutyric acidergic neurons.

Basic fibroblast growth factor (bFGF) is commonly used to enrich and maintain neural stem cells in vitro. Olig2 is an essential transcription factor for oligodendrocyte lineage specification and is expressed predominantly in ventral neuroepithelial cells in the medial and lateral ganglionic eminence (GE), where oligodendrocyte progenitors originate. Here we report significant induction of Olig2 expression in dorsal neuroepithelium-derived cells cultured in the presence of bFGF, in which Olig2-expressing cells were initially negligible. Among Olig2-expressing cells appearing after a 5-day treatment with bFGF, 99.8% coexpressed nestin. There was no significant difference in proliferation or apoptosis in dorsal and ventral neuroepithelial cultures in the presence of bFGF, suggesting that bFGF induces ectopic expression of Olig2 in dorsal "cortical" neuroepithelial cells. Similarly, expression of Mash1, another ventral neuroepithelial cell marker gene, was also induced in cultured dorsal neuroepithelial cells in the presence of bFGF. Conversely, in this culture, expression of dorsal neuroepithelial cell markers, such as Neurogenin1, Neurogenin2, Pax6, and Emx2, was down-regulated. These results suggested a possible ventralizing activity of bFGF. In fact, bFGF-treated dorsal neuroepithelial cells acquired the potential to generate O4-positive oligodendrocytes with efficacy comparable to that observed with GE-derived cells. In marked contrast, bFGF did not enable dorsal neuroepithelial cells to generate gamma-aminobutyric acid (GABA) neurons, which normally develop only from GE in vivo. Thus, bFGF endows dorsal telencephalic neural progenitors with the ability to differentiate into oligodendrocytes but not GABAergic neurons, suggesting the presence of different mechanisms governing specification of dorsoventral cell identities of neuronal and glial cell lineages.

Animals↗

Neuroepithelial stem cells from the embryonic spinal cord: isolation, characterization, and clonal analysis.

Adherent cultures of E10.5 rat neuroepithelial cells (NEP cells) from the caudal neural tube require FGF (fibroblast growth factor) and CEE (chick embryo extract) to proliferate and maintain an undifferentiated phenotype in culture. Epidermal growth factor (EGF) does not support E10.5 NEP cells in adherent culture and NEP cells do not form EGF-dependent neurospheres. NEP cells, however, can be grown as FGF-dependent neurospheres. NEP cells express nestin and lack all lineage-specific markers for neuronal and glial sublineages, retain their pleuripotent character over multiple passages, and can differentiate into neurons, astrocytes, and oligodendrocytes when plated on laminin in the absence of CEE. In clonal culture, NEP cells undergo self-renewal and generate colonies that vary in size from single cells to several thousand cells. With the exception of a few single-cell clones, all other NEP-derived clones contain more than one identified phenotype, with over 40% of the colonies containing A2B5, beta-111 tubulin, and GFAP-immunoreactive cells. Thus, NEP cells are multipotent and capable of generating multiple neural derivatives. NEP cells also differentiate into motoneurons immunoreactive for choline acetyl transferase (ChAT) and the low-affinity neurotrophin receptor (p75) in both mass and clonal culture. Double labeling of clones for ChAT and glial, neuronal, or oligodendrocytic lineage markers shows that motoneurons always arose in mixed cultures with other differentiated cells. Thus, NEP cells represent a common progenitor for motoneurons and other spinal cord cells. The relationship of NEP cells with other neural stem cells is discussed.

Animals↗

Lineage restriction of neuroepithelial precursor cells from fetal human spinal cord.

In the presence of epidermal growth factor (EGF) and/or fibroblast growth factor 2 (FGF2), neuroepithelial precursor cells from dissociated fetal human spinal cord are mitotically active and form free-floating spheres of undifferentiated cells. Proliferating cells were obtained in approximately 40% of preparations with each mitogen, were immunoreactive for the intermediate filament nestin, and did not express neuronal- or glial-specific markers. Early passage neuroepithelial precursor cells were pluripotent and differentiated into neurons expressing MAP2a,b, NF-M, and TuJ1, and GFAP-positive astrocytes; however, oligodendrocytes were never seen. As the cells were passaged from P0 to P4, the percentage of differentiating neurons significantly decreased and the prevalence of astrocytes significantly increased. While the majority of cell populations from individual preparations stopped proliferating between 3 and 6 passages, two expanding cell lines have been successfully expanded in EGF and FGF2 for over 25 passages and have been maintained in culture for over one year. These cells express nestin and not other cell-specific lineage markers. When differentiated, these neuroepithelial cell lines differentiate only into astrocytes, showing no expression of any neuronal marker. These data suggest that continued passage under these conditions preferentially selects for spinal cord neural precursors that are restricted to the astrocytic lineage. Despite the lineage restriction of later passage cell populations, these results provide a rationale for future investigation into the lineage potential of these cells in vivo following transplantation into the adult CNS, potentially as a therapeutic approach for traumatic injury and neurodegenerative disease.

Adult↗

Retinal regeneration in teleost fish.

The neural retina in teleost fish can regenerate after surgical or neurotoxic destruction. Whereas in amphibians the retina regenerates by transdifferentiation of pigmented retinal epithelial cells, in goldfish (Carassius auratus) the source of regenerated retinal cells is a population of scattered proliferating cells located in the outer nuclear layer within the differentiated retina. These proliferating cells are modified neuroepithelial cells termed 'rod precursors' because in the intact retina they produce only rod photoreceptor cells and do so continuously, inserting new rods into the growing adult retina. Although rod precursors normally exhibit a restricted developmental fate they appear not to be committed to the rod lineage. When retinal neurons are destroyed, rod precursors cease producing rods and give rise to clusters of primitive neuroepithelial cells which divide vigorously and reconstitute the retina in an orderly temporal pattern that mimics the process of normal development. Only after production of cones and other retinal neurons has ceased do rod precursors again appear and resume the generation of rods. We conclude that rod precursors respond to local cues in their environment that regulate the differentiation and choice of cell fate by their progeny.

Animals↗

A reexamination of the role of microfilaments in neurulation in the chick embryo.

Formation of wedge-shaped neuroepithelial cells, owing to the constriction of apical bands of microfilaments, is widely believed to play a major part in bending of the neural plate. Although cell "wedging" occurs during neurulation, its exact role in bending is unknown. Likewise, although microfilament bands occupy the apices of neuroepithelial cells, whether these structures are required for cell wedging is unknown. Finally, although it is known that cytochalasins interfere with neurulation, it is unknown whether they block shaping or furrowing of the neural plate, or elevation, convergence, or fusion of the neural folds. The purpose of this study was to reexamine the role of microfilaments in neurulation in the chick embryo. Embryos were treated with cytochalasin D (CD) to depolymerize microfilaments and were analyzed 4-24 hr later. CD did not prevent neural plate shaping, median neural plate furrowing, wedging of median neuroepithelial cells, or neural fold elevation. However, dorsolateral neural plate furrowing, wedging of dorsolateral neuroepithelial cells, and convergence of the neural folds were blocked frequently by CD. In addition, neural folds always failed to fuse across the midline in embryos treated with CD, and neural crest cell migration was prevented. These data indicate that only the later aspects of neurulation may require microfilaments, and that certain neuroepithelial cells, particularly those that normally wedge with median furrowing and elevation of the neural folds, become (and remain) wedge-shaped in the absence of apical microfilament bands. Thus, microfilament-mediated constriction of neuroepithelial cell apices is not the major force for median neuroepithelial cell wedging and elevation of the chick neural plate. Further studies are needed to localize the motor(s) for these processes.

Actin Cytoskeleton↗

Loss of occludin and functional tight junctions, but not ZO-1, during neural tube closure--remodeling of the neuroepithelium prior to neurogenesis.

Neuroepithelial cells can generate nonepithelial cells, the neurons. Here we have investigated, for chick and mouse embryos, the epithelial character of neuroepithelial cells in the context of neurogenesis by examining the presence of molecular components of tight junctions during the transition from the neural plate to the neural tube. Immunoreactivity for occludin, a transmembrane protein specific to tight junctions, was detected at the apical end of the lateral membrane of neuroepithelial cells throughout the chick neural plate. During neural tube closure, occludin disappeared from all neuroepithelial cells. Correspondingly, the addition of horseradish peroxidase to the apical side of the neuroepithelium by injection into the amniotic cavity of mouse embryos revealed the presence of functional tight junctions in the neural plate (Embryonic Day 8), but not the neural tube (Embryonic Day 9). In contrast to occludin, expression of ZO-1, a peripheral membrane protein of tight junctions, increased from the neural plate to the neural tube stage, also being confined to the apical end of the lateral neuroepithelial cell membrane. This localization coincided with that of N-cadherin, whose expression increased concomitantly with the disappearance of occludin. We propose that the loss of tight junctions from neuroepithelial cells reflects an overall decrease in their epithelial nature, which precedes the generation of neurons.

Amnion↗

Grafted swine neuroepithelial stem cells can form myelinated axons and both efferent and afferent synapses with xenogeneic rat neurons.

Neuroepithelial stem cells derived from the swine mesencephalic neural tube were examined regarding their eligibility for neural xenografting as a donor material, with the aim of evaluating myelinated axon formation and both types of synaptic formation with xenogeneic host neurons as part of possible neural circuit reconstruction. The mesencephalic neural tube tissues were dissected out from swine embryos at embryonic days 17 and 18 and were implanted immediately into the striatum of the Parkinsonian model rat. The swine-derived grafts had many nestin-positive rosette-forming, neurofilament-positive, and tyrosine hydroxylase-positive cells in the rat striatum. Electron microscopic study revealed both efferent and afferent synaptic formations in the donor-derived immature neurons or tyrosine hydroxylase-positive donor cells in the grafts. Myelinated axons, both positive and negative for swine-specific neurofilament antibody, were mingled together in the graft. These results indicated that implanted neuroepithelial stem cells could survive well and divide asymmetrically into both nestin-expressing precursors and differentiated neurochemical marker-expressing neurons in the xenogeneic rat striatum, with the help of an immunosuppressant. Donor-derived immature neurons formed both efferent and afferent synapses with xenogeneic host neurons, and donor-derived axons were myelinated, which suggests that implanted swine neuroepithelial stem cells could possibly restore damaged neuronal circuitry in the diseased brain.

Animals↗

Platelet-derived growth factor induces chemotaxis of neuroepithelial stem cells.

The ability of differentiating cells to migrate within the developing central nervous system (CNS) depends on extrinsic guidance signals, some of which are growth factors. In this study we have investigated the chemotactic response of cultured stem cells from the embryonic rat cortex to platelet-derived growth factor (PDGF). Nestin-positive stem cells from the developing CNS can be maintained and expanded in vitro under serum-free conditions in the presence of basic fibroblast growth factor (bFGF). Northern blot analysis of PDGF receptor expression revealed both alpha- and beta-receptors on bFGF-treated neural stem cells. Both PDGF-AA and PDGF-BB readily induced directed migration of cultured neuroepithelial cells as measured in a microchemotaxis assay. Blocking of the migratory response was achieved by incubation with PDGF isoform-specific antibodies. More than 90% of the migrating cells were nestin-positive and incorporation of BrdU was also seen suggesting the cells to be immature and not yet committed to a specific cell lineage. These findings suggest a role for PDGF in cell migration in the developing cortex.

Animals↗

Neuroepithelial endocrine cells in the lung of Ambystoma mexicanum.

Neuroepithelial endocrine (NEE) cells were for the first time identified in the lung of the entirely aquatic urodele, Ambystoma mexicanum, by using light and electron microscopy, histochemistry, and immunocytochemistry. In the basal part of the ciliated epithelium and, less often, in the respiratory portion of the lung, NEE cells were found to occur both solitarily and in small clusters. No typical neuroepithelial bodies could be found. Using the method of Fernandez Pascual, some NEE cells were found to be argyrophilic. Microspectrofluorimetric analysis of formaldehyde-induced fluorescence and immunocytochemistry revealed the presence of 5-hydroxytryptamine. With antibodies to neuron-specific enolase only a few NEE cells exhibited a faint immunostaining. Electron-microscopically, the NEE cells are provided with distinctive cytoplasmic membrane-bound dense granules of variable size, which gave a positive argentaffin reaction. The images of emiocytotic granule release are indicative of a secretory function. In the tracheal epithelium. NEE cells seem to occur only solitarily. They bear the same ultrastructural characteristics as the intrapulmonary NEE cells but here, the dense granules are larger and associated with numerous bundles of microfilaments. Intraepithelial nerve endings were observed near the airway lumen. Between nerve terminals and NEE cells, synaptic complexes with aggregations of clear-centered vesicles close to the presynaptic membrane thickenings were observed. In addition, some nerve endings from "reciprocal synapses" with NEE cells. A receptosecretory function for NEE cells in the lung of A. mexicanum is supposed.

Ambystoma↗

The developing neuroepithelium in human embryonic and fetal brain studied with vimentin-immunocytochemistry.

The neuroepithelial cells, which constitute the primordium of the CNS, are potentially capable of generating neuronal and glial cell lineages concomitantly. The appearance and morphological development of vimentin-positive neuroepithelial cells in human embryonic and fetal brain (4-16 weeks) were studied with immunocytochemistry. In embryos aged 4-6 weeks, vimentin-reactivity was seen in all neuroepithelial cells, including those which exhibited mitotic figures. The distribution of reactivity changed according to a general developmental pattern, which commenced and proceeded temporally different in various regions of the CNS. All regions exhibited vimentin-positive neuroepithelial cells, the distribution and morphology of which gradually changed, resulting in lamination of the neural wall into two and subsequently three layers. The neocortex and midline raphe were the only regions to differ significantly from the general pattern. When reactivity to glial fibrillary acidic protein developed at 7-8 weeks, the distribution was very much like that of vimentin at the same stage. Reactivity to glial, neuronal and other cellular markers (S-100, neurofilament, neuron specific enolase, desmin, and cytokeratin) revealed different distributions. Although cells retaining vimentin beyond the ventricular zone stage are radial glial cells and presumptive fibrous astrocytes, it seems unlikely that vimentin is a marker for a distinct cell lineage during early CNS development. It is suggested that all neuroepithelial cells in vivo differentiate to a stage where they express vimentin, and that vimentin may have a functional role in cellular movements and during the interkinetic nuclear migration.

Antibodies, Monoclonal↗

Astroglial differentiation from neuroepithelial precursor cells of amphibian embryos: an in vivo and in vitro analysis.

Initial development of astroglial phenotype has been studied in vitro in an amphibian embryo (Pleurodeles waltI), to document the differentiation potentialities acquired by neural precursor cells isolated at the early neurula stage. In particular, we sought to determine whether interactions between neuroepithelial cells and the inducing tissue, the chordamesoderm, are required beyond this stage to specify precursor cells along glial lineages. Glial cell differentiation was documented by examining the appearance of glial fibrillary acidic protein (GFAp), a specific marker of astroglial lineages. Cells expressing GFAp-immunoreactivity differentiated rapidly, after 48 hours of culture, from cultivated neural plate cells, irrespective of the presence or absence of the inducing tissue. The widespread expression of Pleurodeles GFAp protein in neural plate cultures, in which CNS precursor cells develop alone in a simple saline medium, showed that prolonged contact with chordamesodermal cells was not necessary for the emergence of the astroglial phenotype. In addition, the initial development of astroglial phenotype has been defined in vivo. The first detectable GFAp-immunoreactivity was visualized in the neural tube of stage-24 embryos, a stage corresponding to 2-3 days in culture, defining radial glial cell end-feet. Thus, dissociation and culture of neural precursor cells did not appear to modify the onset of astroglial differentiation. At stage 32, GFAp-immunoreactivity was observed over the entire length of radial glial fibers and was also evidenced in mitotic cells located in the ventricular zone, suggesting that radial glial cells were not all post-mitotic.

Animals↗

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.

Animals↗