scholarly journals Thymic B lymphocyte clones from patients with myasthenia gravis secrete monoclonal striational autoantibodies reacting with myosin, alpha actinin, or actin.

1986 ◽  
Vol 164 (4) ◽  
pp. 1043-1059 ◽  
Author(s):  
C L Williams ◽  
V A Lennon
Keyword(s):  
Skeletal Muscle ◽  
Epithelial Cells ◽  
Myasthenia Gravis ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
B Lymphocyte ◽  
High Yield ◽  
Thymic Epithelial Cells ◽  
Anchoring Proteins ◽  
Mucosal Cells

Striational autoantibodies (StrAb), which react with elements of skeletal muscle cross-striations, occur frequently in patients with thymoma associated with myasthenia gravis (MG). Dissociated thymic lymphocytes from 22 of 72 MG patients secreted StrAb when cultured with PWM. A high yield of EBV-transformed B cell lines was established from thymus, thymoma, and peripheral blood of seven patients with MG, but clones secreting StrAb arose only from the three patients who had StrAb in their sera. The monoclonal StrAb bound to A bands or I bands in skeletal muscle of human, rat, and frog. One bound to mitochondria in addition to myofibrillar I bands. None bound to nuclei, smooth muscle, or gastric mucosal cells. In immunoblot analyses and ELISAs the monoclonal StrAb bound to muscle and nonmuscle isotypes of myosin, alpha actinin, and/or actin. All bound to contractile proteins common to thymus and muscle, and one selectively immunostained epithelial cells of the thymic medulla. From these antigenic specificities we suggest that StrAb might arise as an immune response directed against the cytoskeletal anchoring proteins associated with nicotinic acetylcholine receptors in thymic epithelial cells undergoing neoplastic transformation to thymoma.

scholarly journals A Striational Muscle Antigen and Myasthenia Gravis-Associated Thymomas Share an Acetylcholine-Receptor Epitope

1992 ◽  
Vol 2 (2) ◽  
pp. 77-84 ◽  
Author(s):  
Alexander Marx ◽  
Mary Osborn ◽  
Socrates Tzartos ◽  
Kerstin I. Geuder ◽  
Berthold Schalke ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Myasthenia Gravis ◽  
Acetylcholine Receptor ◽  
Tumor Antigens ◽  
Molecular Mimicry ◽  
Thymic Epithelial Cells ◽  
Characteristic Finding ◽  
The Common ◽  
Secondary Phenomenon ◽  
Type Ii Fibers

The coincidence of autoantibodies against the acetylcholine receptor (AChR) and muscle striational antigens (SA) is a characteristic finding in thymoma-associated myasthenia gravis (MG), but their origins are still unresolved. Some common muscle antigens that were shown to be targets of anti-SA autoantibodies in thymoma-associated MG have also been detected in normal or neoplastic thymic epithelial cells, suggesting that the release of (eventually altered) antigens from the thymic tumors could elicit SA autoimmunity. In contrast to this model, we report here that titin, which is a recently reported target of SA autoimmunity, is not expressed in thymomas. In addition, we show that skeletal muscle type-II fibers exhibit a striational immunoreactivity with monoclonal antibody mAb155, which was previously identified to label a very immunogenic cytoplasmic epitope of the AChR and neoplastic epithelial cells of MGassociated thymomas. We conclude from these findings that titin autoimmunity in thymoma-associated MG is either due to a molecular mimicry mechanism involving tumor antigens (other than titin) or is a secondary phenomenon following release of titin from muscle. Based on the common immunoreactivity of the AChR, a striational antigen and thymoma, we suggest as the pathogenetic mechanism of thymoma-associated MGa "circulus vitiosus" in which SA autoimmunity could help maintain the AChR autoimmunity that is primarily elicited by the thymomas.

scholarly journals Phosphocholine-Modified Lipooligosaccharides of Haemophilus influenzae Inhibit ATP-Induced IL-1β Release by Pulmonary Epithelial Cells

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1979 ◽  
Author(s):  
Katrin Richter ◽  
Christian Koch ◽  
Alexander Perniss ◽  
Philipp Wolf ◽  
Elke Schweda ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Haemophilus Influenzae ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Opportunistic Pathogen ◽  
Mammalian Host ◽  
Nicotinic Acetylcholine ◽  
Pulmonary Epithelial Cells ◽  
Airway Infections ◽  
Human Lung Carcinoma

Phosphocholine-modified bacterial cell wall components are virulence factors enabling immune evasion and permanent colonization of the mammalian host, by mechanisms that are poorly understood. Recently, we demonstrated that free phosphocholine (PC) and PC-modified lipooligosaccharides (PC-LOS) from Haemophilus influenzae, an opportunistic pathogen of the upper and lower airways, function as unconventional nicotinic agonists and efficiently inhibit the ATP-induced release of monocytic IL-1β. We hypothesize that H. influenzae PC-LOS exert similar effects on pulmonary epithelial cells and on the complex lung tissue. The human lung carcinoma-derived epithelial cell lines A549 and Calu-3 were primed with lipopolysaccharide from Escherichia coli followed by stimulation with ATP in the presence or absence of PC or PC-LOS or LOS devoid of PC. The involvement of nicotinic acetylcholine receptors was tested using specific antagonists. We demonstrate that PC and PC-LOS efficiently inhibit ATP-mediated IL-1β release by A549 and Calu-3 cells via nicotinic acetylcholine receptors containing subunits α7, α9, and/or α10. Primed precision-cut lung slices behaved similarly. We conclude that H. influenzae hijacked an endogenous anti-inflammatory cholinergic control mechanism of the lung to evade innate immune responses of the host. These findings may pave the way towards a host-centered antibiotic treatment of chronic airway infections with H. influenzae.

IDENTIFICATION OF HUMAN THYMIC EPITHELIAL CELLS WITH ANTIBODIES TO THYMOSIN ?1, IN MYASTHENIA GRAVIS

1981 ◽  
Vol 377 (1 Myasthenia Gr) ◽  
pp. 477-485 ◽  
Author(s):  
Marinos C. Dalakas ◽  
W. King Engel ◽  
John E. McClure ◽  
Allan L. Goldstein ◽  
Valerie Askanas
Keyword(s):  
Epithelial Cells ◽  
Myasthenia Gravis ◽  
Thymic Epithelial Cells

A novel alpha conotoxin (α-PIB) isolated from C. purpurascens is selective for skeletal muscle nicotinic acetylcholine receptors

Toxicon ◽  
2007 ◽  
Vol 49 (8) ◽  
pp. 1193-1199 ◽  
Author(s):  
Estuardo López-Vera ◽  
Richard B. Jacobsen ◽  
Michael Ellison ◽  
Baldomero M. Olivera ◽  
Russell W. Teichert
Keyword(s):  
Skeletal Muscle ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Nicotinic Acetylcholine

Other Proven and Putative Autoimmune Disorders of the Peripheral Nervous System

2017 ◽  
Author(s):  
Doris G. Leung
Keyword(s):  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Autoimmune Disorder ◽  
Synaptic Proteins ◽  
Disease Treatment ◽  
Nicotinic Acetylcholine ◽  
System P ◽  
Presynaptic Calcium

Myasthenia gravis is in most cases an autoimmune disorder of the neuromuscular junction in which antibodies are directed at nicotinic acetylcholine receptors or other synaptic proteins, such as the MusK protein that is involved in the formation of the formation and maturation of the motor endplate. Less commonly, myasthenia gravis can result from antibodies directed to presynaptic calcium channels as a side effect of paraneoplastic antibodies (Lambert-Eaton syndrome) or from a developmental paucity of acetylcholine receptors in the neonatal form of the disease. Treatment is usually a combination of aceetylcoholinesterase inhibitors such as pyridostigmine to prolong the life of acetylcholine released at the neuromuscular junction and/or drugs such as corticosteroids aimed at reducing inflammation.

Human and Rodent Bronchial Epithelial Cells Express Functional Nicotinic Acetylcholine Receptors

1998 ◽  
Vol 54 (5) ◽  
pp. 779-788 ◽  
Author(s):  
Arno D. J. Maus ◽  
Edna F. R. Pereira ◽  
Peter I. Karachunski ◽  
Robert M. Horton ◽  
Duraiswamy Navaneetham ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Bronchial Epithelial Cells ◽  
Nicotinic Acetylcholine ◽  
Bronchial Epithelial

Peptide-amidating Enzymes Are Expressed in the Stellate Epithelial Cells of the Thymic Medulla

1998 ◽  
Vol 46 (5) ◽  
pp. 661-668 ◽  
Author(s):  
Alfredo Martínez ◽  
Andrew Farr ◽  
Michele D. Vos ◽  
Frank Cuttitta ◽  
Anthony M. Treston
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Lines ◽  
B Lymphocyte ◽  
Regulatory Peptides ◽  
Convincing Evidence ◽  
Thymic Epithelial Cells ◽  
Thymic Epithelial Cell ◽  
Epithelial Cell Lines ◽  
Amidating Enzymes

C-terminal amidation is a post-translational processing step necessary to convey biological activity to a large number of regulatory peptides. In this study we have demonstrated that the peptidyl-glycine α-amidating monooxygenase enzyme complex (PAM) responsible for this activity is located in the medullary stellate epithelial cells of the thymus and in cultured epithelial cells bearing a medullary phenotype, using Northern blot, immunocytochemistry, in situ hybridization, and enzyme assays. Immunocytochemical localization revealed a granular pattern in the cytoplasm of the stellate cells, which were also positive for cytokeratins and a B-lymphocyte-associated antigen. The presence of PAM activity in medium conditioned by thymic epithelial cell lines suggests that PAM is a secreted product of these cells. Among the four epithelial cell lines examined, there was a direct correlation between PAM activity and content of oxytocin, an amidated peptide. Taken together, these data provide convincing evidence that thymic epithelial cells have the capacity to generate amidated peptides that may influence T-cell differentiation and suggest that the amidating enzymes could play an important role in the regulation of thymic physiology.

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