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At least 235 records · Page 13Linked to original sources
PubMed2001

Interaction of Bordetella pertussis with mast cells, modulation of cytokine secretion by pertussis toxin.

Together with macrophages and dendritic cells, mast cells have recently been shown to interact with certain pathogenic bacteria and present microbial antigens to the immune system. We show here that Bordetella pertussis can adhere to and be phagocytosed by mast cells. In addition, mast cells are able to process and present B. pertussis antigens to T lymphocytes. Furthermore, exposure of mast cells to B. pertussis induced the release of the proinflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6). The release of IL-6 was strongly reduced by pertussis toxin expressed by B. pertussis. The production of IL-10, but not that of IL-4, by mast cells was also inhibited by pertussis toxin. Depletion of mast cells in vivo resulted in significant reduction of early TNF-alpha production in bronchoalveolar lavage (BAL) fluids of B. pertussis-infected mice. These data suggest that mast cells may play a role in the induction of immune responses against B. pertussis through the release of cytokines, especially TNF-alpha.

Animals↗
PubMed1992

Pertussis toxin non-sensitive G protein mediates cholinergic stimulation for secretion of pancreastatin and somatostatin from QGP-1N cells.

To clarify the possible role of a guanine nucleotide-binding protein (G-protein) in the signal transducing system activated by carbachol, actions of carbachol on human pancreastatin producing cell line (QGP-1N) were compared with those of fluoride, a well-known activator of stimulatory (Gs) or inhibitory (Gi) G protein. 10(-5) M of carbachol as well as 20 mM of NaF stimulated secretion of pancreastatin and somatostatin and intracellular Ca2+ mobilization. These secretion and Ca2+ mobilization were not modified by pertussis toxin, an inhibitor of Gi protein. These results suggest that pancreastatin and somatostatin secretions from QGP-1N are regulated by acetylcholine through a muscarinic receptor coupled to the activation of polyphosphoinositide breakdown by a G protein, which appears to be fluoride sensitive but is other than a Gi-like protein.

Calcium↗
PubMed1990

Neuronal influence on intestinal transport.

Reflex activation of the enteric nervous system (ENS) from the intestinal lumen and also from the serosa induces intestinal secretion. Thus mechanical distention, cholera toxin, heat-stable enterotoxin from E. coli, bile acids, mucosal inflammation and chemical peritonitis all induce an intestinal secretion that is inhibited by 60-100% by nerve-blocking agents. As a result of a large number of in vitro and in vivo studies, a picture of the organization of the secretory enteric nervous reflexes is now emerging. In secretory states with preserved intact intestinal epithelium, it is proposed that the reflex activation occurs via stimulation of receptor cells, i.e. epithelial endocrine cells such as EC and N-cells, which release peptides/amines into the interstitial space and thereby activate nerves close to the epithelium. The afferent neurones appear to transfer the reflex to the myenteric plexus, probably by using tachykinins as transmitters. This is in agreement with a superior and co-ordinating role for the myenteric plexus in the control of intestinal function by the ENS. Interneurones in turn mediate the transmission of the nerve signal to the submucosal plexus and the efferent neurones via cholinergic, nicotinic postganglionic receptors. The transmitters at the effector cells are acetylcholine and probably VIP.

Afferent Pathways↗
PubMed1999

Nutrient tasting and signaling mechanisms in the gut. II. The intestine as a sensory organ: neural, endocrine, and immune responses.

The lining of the gastrointestinal tract is the largest vulnerable surface that faces the external environment. Just as the other large external surface, the skin, is regarded as a sensory organ, so should the intestinal mucosa. In fact, the mucosa has three types of detectors: neurons, endocrine cells, and immune cells. The mucosa is in immediate contact with the intestinal contents so that nutrients can be efficiently absorbed, and, at the same time, it protects against the intrusion of harmful entities, such as toxins and bacteria, that may enter the digestive system with food. Signals are sent locally to control motility, secretion, tissue defense, and vascular perfusion; to other digestive organs, for example, to the stomach, gallbladder, and pancreas; and to the central nervous system, for example to influence feeding behavior. The three detecting systems in the intestine are more extensive than those of any other organ: the enteric nervous system contains on the order of 10(8) neurons, the gastroenteropancreatic endocrine system uses more than 20 identified hormones, and the gut immune system has 70- 80% of the body's immune cells. The gastrointestinal tract has an integrated response to changes in its luminal contents. When this response is maladjusted or is overwhelmed, the consequences can be severe, as in cholera intoxication, or debilitating, as in irritable bowel syndrome. Thus it is essential to obtain a full understanding of the sensory functions of the intestine, of how the body reacts to the information, and of how neural, hormonal, and immune signals interact.

Animals↗
PubMed2004

Infection by Shiga toxin-producing Escherichia coli: an overview.

Shiga toxin-producing Escherichia coli (STEC), especially of serotype O157:H7, cause a zoonotic food or waterborne enteric illness that is often associated with large epidemic outbreaks as well as the hemolytic uremic syndrome (HUS), the leading cause of acute renal failure in children. After ingestion, STEC colonize enterocytes of the large bowel with a characteristic attaching and effacing pathology, which is mediated by components of a type III secretion apparatus encoded by the LEE pathogenicity island. Shiga toxins are translocated from the bowel to the circularoty system and transported by leukocytes to capillary endothelial cells in renal glomeruli and other organs. After binding to the receptor globotriaosylceramide on target cells, the toxin is internalized by receptor-mediated endocytosis and interacts with the subcellular machinery to inhibit protein synthesis. This leads to pathophysiological changes that result in HUS. Specific therapeutic or preventive strategies are presently not available. The recent sequencing of genomes of two epidemic E. coli O157 strains has revealed novel pathogenicity islands which will likely provide new insights into the virulence of these bacteria.

Animals↗
PubMedDate not supplied

Giardiasis: host-pathogen biology.

Giardiasis is the most common waterborne diarrheal disease in the United States and is highly prevalent throughout the world. The clinical spectrum of disease ranges from asymptomatic infection to persistent severe malabsorption. The precise interaction between Giardia and its human host remains conjectural because of the paucity of published studies that address the details of its pathogenesis. The immune system of the host responds to this protozoan parasite, and the intestinal epithelium is a site of interaction between parasite and host. Possible mechanisms whereby Giardia may alter the host's absorption of nutrients at the epithelial level include direct physical interference, toxin secretion, direct physical alteration of the epithelium, competition for nutrients, induction of an inflammatory response, and coincidental infection of the host with a second organism. The host's immune system may play both a protective and a pathogenic role.

Adult↗
PubMed2026

Systematic analysis of the type VII secretion system in Streptococcus gallolyticus subsp. gallolyticus reveals genomic diversity and functional associations.

Streptococcus gallolyticus subsp. gallolyticus (Sgg) is an opportunistic pathobiont associated with bacteremia, infective endocarditis, and colorectal cancer. However, the genomic diversity of this subspecies and the distribution of key virulence determinants, particularly the type VII secretion system (T7SS), remain poorly characterized. Here, we performed genomic analyses of 76 Sgg strains from diverse geographic and host origins. Core- and pan-genome analyses, multi locus sequence typing, and phylogenetic reconstruction revealed dominant sequence types (STs) that correlate with geographic origin or source of isolation. Furthermore, systematic characterization of the T7SS locus identified five new T7SS subtypes and demonstrated a strong association between T7SS subtype and ST. We further expanded the known repertoire of T7SS LXG domain-containing polymorphic toxins (LXG toxins) in Sgg substantially through genome-wide searches. Distinct distribution patterns were observed for the LXG toxins across the strains. Lastly, our data indicated that T7SS subtype was significantly associated with biofilm formation capacity of Sgg strains. Together, these findings advance our understanding of Sgg genomic diversity, reveal substantial lineage-associated variation in T7SS architecture and effector repertoires, and suggest a previously unrecognized connection between T7SS and biofilm formation in Sgg.

LXG toxins↗
PubMed1981

Release of vasoactive intestinal polypeptide from the cat small intestine exposed to cholera toxin.

During a four hour observation period vasoactive intestinal polypeptide (VIP) is released in increasing amounts from the feline small intestine exposed to cholera toxin. As VIP is known to be located almost exclusively in the intestinal nerves, the present findings strongly suggest that cholera toxin activates the enteric nervous system. The findings of this and other studies performed in this laboratory lead to the proposal that the choleraic secretion is, at least in part, secondary to the activation of intramural nervous reflexes in the gut.

Animals↗
PubMed1992

Systemic and mucosal antibody responses to toxin A in patients infected with Clostridium difficile.

The systemic and mucosal humoral response to toxin A, the primary virulence factor of Clostridium difficile, was measured in sera and intestinal secretions from 21 patients with C. difficile diarrhea, 9 asymptomatic C. difficile fecal excretors, and 10 noncolonized control subjects. Toxin A-specific IgG was higher in convalescent sera of the patients with diarrhea (mean +/- SE, 990 +/- 260 ng/mL) than in acute sera (620 +/- 150 ng/mL), in sera from asymptomatic excretors (410 +/- 140 ng/mL), or control subjects (320 +/- 50 ng/mL; P < .05 convalescent vs. control). The pattern of toxin A-specific serum IgA and intestinal secretory IgA levels was similar to that of serum IgG in these groups. Neutralization of toxin A was demonstrated in 5 of 14 convalescent sera but only 1 of 13 acute sera (P = .04). However, the presence of neutralizing activity was independent of the subsequent clinical response. Therefore, most patients convalescent from C. difficile diarrhea demonstrate systemic and mucosal antibodies to toxin A, but these antibodies following natural infection do not appear to alter the clinical course of C. difficile infection.

Adult↗
PubMed2004

Monoclonal antibodies and sandwich ELISA for quantitation of HM-1 killer toxin.

To establish a method for quantitative analysis of HM-1 killer toxin (HM-1), two purified mouse monoclonal antibodies, 1F1 and 4A2, and rabbit polyclonal antiserum against HM-1 were prepared. Both monoclonal antibodies were classified as IgG1(kappa) subtype, and did not neutralize the killing activity of HM-1. By SPOTs analysis, the epitope of 1F1 was found in the sequence of CDPNTG with a corresponding sequence of 11-16 from N-terminal amino acid residues of HM-1, but the epitope of 4A2 was not determined. Using 4A2 and polyclonal antiserum, the sandwich enzyme-linked immunosorbent assay (ELISA) was applied to establish the quantitative determination of HM-1. The concentration of HM-1 was determined successfully at the range of 2.5-100 ng/ml. But in the case of 1F1, the method was not established. Genes were constructed to apply the system to the measurement of the secreted concentrations of mutant HM-1, and it was evident that the production of mutant toxins varied among HM-1 mutant genes. The findings of this study are unique in determinimg the epitope of monoclonal antibody against HM-1, and in quantifying the HM-1 using the spot analysis and sandwich ELISA methods.

Animals↗
PubMed1991

Dietary exposure to the trichothecene vomitoxin (deoxynivalenol) stimulates terminal differentiation of Peyer's patch B cells to IgA secreting plasma cells.

The effects of 8 weeks of dietary exposure to the fungal toxin vomitoxin (25 ppm) on the kinetics of in vitro immunoglobulin (Ig) production and appearance of IgA-secreting cells in lymphocyte culture were assessed in the B6C3F1 mouse. The feeding regimen resulted in an IgA:IgG serum ratio of 2.4 compared to 0.4 in controls indicating that there was dysregulation of IgA production in the systemic compartment. Prior toxin feeding had no effect on viability of Peyer's patch (PP) or splenic lymphocyte cultures. IgA production, as determined by enzyme-linked immunosorbent assay, was significantly greater in treatment PP and splenic lymphocytes cultured for 2-11 days than in corresponding controls. Similar trends were found for IgG production in PP cultures although levels were much lower. There were 1.7 and 2.0 times more IgA-producing cells, as measured by the ELISPOT assay, in freshly prepared PP and splenic lymphocytes from treatment mice compared to control mice, respectively. In contrast, after 2 days there were 10.9, 3.2, and 12.4 times more IgA-secreting cells in concanavalin A (Con A), LPS, and unstimulated treatment PP cultures, respectively, and 4.0, 2.0, and 3.5 times times more IgA-secreting cells in 2-day treatment spleen cultures, respectively. Both IgA and IgG secretion in Con A-stimulated cultures were significantly greater when treatment T cells and control B cells were combined than when control T cells and control B cells were combined. Increased Ig secretion attributable to T cell effects was not observed in LPS-stimulated or unstimulated PP reconstitution cultures or in spleen reconstituted cultures with and without mitogen. The results provide evidence that dietary vomitoxin enhances terminal differentiation of IgA secreting cells in PP. This and resultant migration of IgA secreting cells into the systemic compartment favor a shift from IgG to IgA as the primary serum isotype.

Animals↗
PubMed1978

Cholera toxin effects on fluid secretion, adenylate cyclase, and cyclic AMP in porcine small intestine.

The effects of cholera toxin on mucosal cyclic nucleotide concentrations and on net fluid secretion in the porcine small intestine are reported. Cholera toxin causes net secretion of fluid into the small intestine of weanling pigs, and secretory rates are dependent on the dose of the toxin placed in intestinal loops. Intestinal secretion due to cholera toxin exposure was not consistently accompanied by elevated concentrations of mucosal cyclic AMP or cyclic GMP. Net fluid fluxes in individual loops did not correlate with mucosal cyclic AMP concentration in the same loop. Jejunal adenylate cyclase was activated to a lesser extent in pigs, compared with rabbits, after in vivo treatment with cholera toxin. In vitro activation in cell-free homogenates was similar for both species. Papaverine was similar to cholera toxin in causing fluid secretion without cyclic AMP accumulations, but 3-isobutyl-1-methyl xanthine significantly increased cyclic AMP concentration and induced fluid secretion in pigs. Weanling pigs appeared to differ from rabbits in having a secretory response to cholera toxin which was independent of elevations in total mucosal cyclic AMP concentration.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Adaptation of a conjugal transfer system for the export of pathogenic macromolecules.

Conjugal transfer of bacterial plasmids requires a pore through which DNA can traverse the envelopes of the donor and recipient cells. Recent studies indicate that these pores, which are composed of approximately ten proteins, are evolutionarily related to the transport systems required for the transfer of oncogenic T-DNA from Agrobacterium tumefaciens to plant cells and for toxin secretion from Bordetella pertussis.

Bacterial Proteins↗
PubMed1984

Islet-activating protein (IAP)-induced adrenergic modulation of pancreatic A and B cell in dogs.

Islet-activating protein (IAP) is a substance purified from the culture medium of Bordetella pertussis, and its main action is characterized by the enhancement of secretory response to glucose and other stimuli in pancreatic islet. In this experiment, the effect of IAP on epinephrine-induced secretion of immunoreactive insulin (IRI) and glucagon (IRG) was investigated in normal dogs. Epinephrine suppressed IRI secretion and it had a little increment to IRG secretion in control group, while IRI and IRG secretions were significantly increased by epinephrine in IAP pretreated group. Using beta-blocker (Propranolol) with epinephrine, these increments of IRI and IRG secretions in IAP pretreated group were abolished. However, using alpha-blocker (Phentolamine) with epinephrine, these secretions of IRI and IRG in IAP pretreated group were much more increased than epinephrine alone induced secretions. Blood glucose levels were lower in IAP pretreated group than in control group throughout the loading tests in all of the experiments. These findings suggest that (1) IAP decreases blood glucose level and (2) IAP enhances epinephrine-induced secretion of insulin and glucagon by acceleration of beta-adrenergic effect and by reduction of alpha-adrenergic suppression in dogs.

Animals↗
PubMed1999

Role of actin depolymerization in the surfactant secretory response of alveolar epithelial type II cells.

Alveolar epithelial type II cells (AET2) respond with exocytosis of surfactant containing lamellar bodies to stimulation with mechanical stretch and secretagogues, a process that is fundamental for maintaining alveolar stability and lung gas exchange. In the present study in cultured rat AET2, we employed botulinum C2 toxin, a binary toxin which ADP ribosylates nonmuscle G-actin, as a specific tool to probe the role of the actin microfilament system in the surfactant secretory process. Incubation of AET2 with C2 toxin caused a dose-dependent decay of the cellular F-actin content to a minimum of 20% of baseline, concomitant with an increase in monomeric actin. In parallel, a significant augmentation of baseline surfactant secretion up to twofold elevated levels above control was noted, as assessed by the release of prelabeled phosphatidylcholine. Pretreatment with phalloidin, which stabilized F-actin and reduced the level of G-actin, prevented the C2 toxin-elicited enhancement of baseline surfactant secretion. Even low C2 toxin concentrations, resulting in a reduction of total cellular F-actin content of approximately 10%, sufficed to augment secretagogue (ATP) and, more impressively, mechanical stress elicited an increase in surfactant secretion; the response to the biophysical challenge more than doubled. When investigated in the absence of toxin, different secretagogues (ATP, phorbol ester, betamimetics) caused a rapid-onset, transient reduction of F-actin in the range between 15 and 25% as a consistent part of their secretory response pattern. These data suggest that the state of actin polymerization is intimately linked to the exocytosis process underlying surfactant secretion in AET2. Microfilament system-related compartmentalization effects and/or or the impact of the state of actin assembly on signaling events may be considered as underlying events.

Actins↗
PubMed2000

Sensitivity of embryonic rat dorsal root ganglia neurons to Clostridium botulinum neurotoxins.

Clostridium botulinum neurotoxins (BoNT) are zinc dependent endopeptidases which, once internalised into the neuronal cytosol, block neurotransmission by proteolysis of membrane-associated proteins putatively involved in synaptic vesicle docking and fusion with the plasma membrane. Although many studies have used a variety of cellular systems to study the neurotoxins, most require relatively large amounts of toxin or permeabilisation to internalise the neurotoxin. We present here a primary culture of embryonic rat dorsal root ganglia (DRG) neurons that exhibits calcium-dependent substance P secretion when depolarised with elevated extracellular potassium and is naturally BoNT sensitive. The DRG neurons showed a different IC50 for each of the toxins tested with a 1000 fold difference between the most and least potent neurotoxins (0.05, 0.3, 30 and approximately 60 nM for A, C, F and B, respectively). BoNT/A cleavage of SNAP-25 was seen as early as 2 h, but substance P secretion was not significantly inhibited until 4 h intoxication and the effects of BoNT/A were observed for as long as 15 days. This primary neuronal culture system represents a new and sensitive cellular model for the in vitro study of the botulinum neurotoxins.

Animals↗