Intestinal anaphylaxis: in vivo and in vitro studies of the rat proximal colon

1988 ◽  
Vol 255 (2) ◽  
pp. G201-G205 ◽  
Author(s):  
D. Forbes ◽  
M. Patrick ◽  
M. Perdue ◽  
A. Buret ◽  
D. G. Gall
Keyword(s):  
Mast Cell ◽  
Immunoglobulin E ◽  
Short Circuit ◽  
Proximal Colon ◽  
Antigen Challenge ◽  
Food Protein ◽  
Ussing Chambers ◽  
Cl Secretion ◽  
Ige Mediated

The response of the rat proximal colon to an immunoglobulin E (IgE)-mediated hypersensitivity reaction was examined. Rats were sensitized to egg albumin (EA) by intraperitoneal injection, and serum titers of specific anti-EA IgE were measured at 14 days. Sensitized animals had titers of greater than or equal to 1:64, whereas no anti-EA IgE antibodies were detected in controls. Water and electrolyte absorption in the proximal colon, before and during antigen challenge, was measured by in vivo marker perfusion. Antigen challenge resulted in significant inhibition of water, Na+, Cl-, and K+ absorption in vivo. Proximal colonic tissue from sensitized and control animals was studied in Ussing chambers under short-circuited conditions. Antigen challenge of sensitized tissue resulted in significant increases in short-circuit current due to the induction of active Cl- secretion. No such changes were seen in control tissue. The abnormalities induced by antigen challenge in tissue from sensitized animals was blocked by doxantrazole (10(-3) M), a mast cell stabilizer. The findings indicate that IgE-mediated reactions in rat proximal colon to a food protein cause pertubations in water and electrolyte transport secondary to active Cl- secretion and these abnormalities appear to be due to mast cell degranulation.

NaCl transport across equine proximal colon and the effect of endogenous prostanoids

1990 ◽  
Vol 259 (1) ◽  
pp. G62-G69 ◽  
Author(s):  
L. L. Clarke ◽  
R. A. Argenzio
Keyword(s):  
Ion Transport ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Proximal Colon ◽  
Nacl Transport ◽  
Apparent Lack ◽  
Ussing Chambers ◽  
Cl Secretion

In contrast to in vivo findings, the equine proximal colon fails to demonstrate significant net absorption of Na+ and Cl- under in vitro conditions. The present study was undertaken to determine if endogenous prostanoids are responsible for this apparent lack of ion transport. Proximal colonic tissues from ponies were preincubated in either normal Ringer solution or in Ringer containing 1 microM indomethacin and studied in Ussing chambers containing these solutions. Untreated colonic mucosa demonstrated negligible Na(+)-Cl- absorption in the basal state. In contrast, indomethacin-treated colon significantly absorbed Na+ and Cl-, primarily as the result of an equivalent increase in the mucosal-to-serosal flux of these ions. Preincubation of proximal colon in 0.1 mM ibuprofen-treated Ringer yielded similar results. Treatment of indomethacin colon with 1 mM mucosal amiloride eliminated net Na(+)-Cl- absorption without affecting the short-circuit current (Isc). The Isc in control tissue was significantly greater than in indomethacin-treated tissue and was reduced by 0.1 mM serosal furosemide. Serosal addition of 0.1 microM prostaglandin E2 or 10 mM serosal plus mucosal theophylline to indomethacin-treated tissues abolished net Na(+)-Cl- absorption and increased the Isc to levels indistinguishable from control. In contrast, control tissues were essentially unaffected by these secretagogues. These findings indicated that Na(+)-Cl- absorption in equine proximal colon was electroneutral (possibly involving Na(+)-H+ exchange) and that the tissue was capable of electrogenic Cl- secretion. However, under the in vitro conditions, basal ion transport was dominated by endogenous prostanoids that abolished Na(+)-Cl- absorption and elicited near-maximal electrogenic Cl- secretion.

Intestinal anaphylaxis in the rat: jejunal response to in vitro antigen exposure

1986 ◽  
Vol 250 (4) ◽  
pp. G427-G431 ◽  
Author(s):  
M. H. Perdue ◽  
D. G. Gall
Keyword(s):  
Mast Cell ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Secretory Process ◽  
Mucosal Mast Cell ◽  
Food Protein ◽  
Egg Albumin ◽  
Ussing Chambers

In previous studies we showed that rats sensitized to egg albumin respond to in vivo intraluminal antigen with decreased net absorption of Na+, Cl-, and water. These abnormalities are associated with high serum levels of immunoglobulin E (IgE) antibodies and mucosal mast cell degranulation. In the present in vitro study electrical parameters, unidirectional fluxes of Na+ and Cl-, and levels of cAMP were determined in jejunum from sensitized and control rats during a basal period and after antigen addition. In Ussing chambers potential difference and short-circuit current increased significantly in tissue from sensitized rats after addition of 100 micrograms/ml of egg albumin to both mucosal and serosal surfaces. These changes were accompanied by a reversal of net Cl- absorption to net Cl- secretion. The presence of doxantrazole, a mast cell-stabilizing agent, in the buffer prevented these abnormalities. No changes occurred in response to antigen challenge in tissue from controls. In a further series of experiments the antigen was added only to the mucosal side of the tissue in Ussing chambers. In these studies short-circuit current increased after a lag period of approximately 25 min and was significantly increased (P less than 0.025) at 35 min. cAMP levels increased significantly in jejunal slices from sensitized rats exposed to antigen for 2 min. Our findings suggest that the in vivo transport abnormalities induced by IgE-mediated mucosal reactions to a food protein are related to antigen stimulation of a Cl- secretory process.

Bioelectric properties of cultured epithelial monolayers from distal lung of 18-day fetal rat

1992 ◽  
Vol 262 (5) ◽  
pp. L628-L636 ◽  
Author(s):  
P. M. Barker ◽  
A. D. Stiles ◽  
R. C. Boucher ◽  
J. T. Gatzy
Keyword(s):  
Short Circuit ◽  
In Vivo Studies ◽  
Fetal Life ◽  
Pulmonary Epithelium ◽  
Fresh Tissue ◽  
Fetal Sheep ◽  
Ussing Chambers ◽  
Cl Secretion ◽  
Fetal Rat

In vivo studies of fetal sheep suggest that the liquid present in the lumen of the lung throughout fetal life is derived from Cl- secretion by the pulmonary epithelium. Monolayer preparations of enriched epithelial cells from distal fetal rat (18-day gestation) lung, grown in serum-free media, were histologically similar to acinar (prealveolar) structures of fresh tissue. In Ussing chambers, basal transepithelial potential difference (PD), calculated equivalent short-circuit current (Ieq), and transepithelial resistance (R) were 4.4 +/- 0.3 mV (matrix positive), 35.6 +/- 1.6 microA/cm2, and 120.0 +/- 4.0 omega cm2, respectively. Ouabain (10(-3) M) eliminated 57% of basal Ieq within 30 min, amiloride (10(-4) M) induced a 13% fall in Ieq, and phlorizin (10(-4) M) had no effect on bioelectric properties. Diphenylamine-2-carboxylate (DPC, 3 x 10(-3) M) inhibited Ieq by 50%. Bumetanide had no effect on baseline bioelectric parameters. The hyperpolarization that accompanied apical or bilateral replacement of Cl- and was enhanced by terbutaline suggested an apical Cl- permselectivity. Effects of Na+ replacement on amiloride-pretreated monolayers were consistent with Na(+)-dependent Cl- secretion or amiloride-insensitive pathways. Under these growth conditions, this preparation exhibits bioelectric characteristics that are compatible with Cl- secretion and Na+ absorption. The mechanism of Cl- secretion may be similar to that of airways but is uniquely bumetanide insensitive.

Effects of amphotericin B on ion and fluid movement across dog tracheal epithelium

1983 ◽  
Vol 55 (4) ◽  
pp. 1257-1261 ◽  
Author(s):  
I. Nathanson ◽  
J. H. Widdicombe ◽  
J. A. Nadel
Keyword(s):  
Amphotericin B ◽  
Short Circuit ◽  
Open Circuit ◽  
Tracheal Epithelium ◽  
Fluid Movement ◽  
Ussing Chambers ◽  
Cl Secretion ◽  
Special Apparatus ◽  
Net Fluxes

Ion fluxes or fluid flow were measured across sheets of dog tracheal epithelium mounted in Ussing chambers or a special apparatus, respectively. Under short-circuit conditions, luminal amphotericin B (3 X 10(-5) M) caused an inhibition of net Cl secretion and an increase in net Na absorption across paired tissues. In paired tissues under resting open-circuit conditions, there was no significant net transepithelial flux of either Cl or Na. Amphotericin B induced significant net fluxes of both Cl and Na toward the serosal side. In separate tissues from the same animals, there was no significant transepithelial fluid movement under resting conditions. Amphotericin B caused a net absorption of fluid. The absorption of salt and fluid in amphotericin B-treated tissues was abolished by ouabain. We conclude that stimulation of active Na transport by amphotericin B leads to fluid absorption. In vivo, the movement of fluid across the dog tracheal epithelium may be dependent on a balance between active Cl secretion and active Na absorption.

scholarly journals The transcriptional program, functional heterogeneity, and clinical targeting of mast cells

2017 ◽  
Vol 214 (9) ◽  
pp. 2491-2506 ◽  
Author(s):  
Gökhan Cildir ◽  
Harshita Pant ◽  
Angel F. Lopez ◽  
Vinay Tergaonkar
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Immunoglobulin E ◽  
Inflammatory Diseases ◽  
Small Population ◽  
Transcriptional Program ◽  
Cell Functions ◽  
New Concepts ◽  
Health And Disease ◽  
Ige Mediated

Mast cells are unique tissue-resident immune cells that express an array of receptors that can be activated by several extracellular cues, including antigen–immunoglobulin E (IgE) complexes, bacteria, viruses, cytokines, hormones, peptides, and drugs. Mast cells constitute a small population in tissues, but their extraordinary ability to respond rapidly by releasing granule-stored and newly made mediators underpins their importance in health and disease. In this review, we document the biology of mast cells and introduce new concepts and opinions regarding their role in human diseases beyond IgE-mediated allergic responses and antiparasitic functions. We bring to light recent discoveries and developments in mast cell research, including regulation of mast cell functions, differentiation, survival, and novel mouse models. Finally, we highlight the current and future opportunities for therapeutic intervention of mast cell functions in inflammatory diseases.

Active electrolyte transport in mammalian buccal mucosa

1988 ◽  
Vol 255 (3) ◽  
pp. G286-G291 ◽  
Author(s):  
R. C. Orlando ◽  
N. A. Tobey ◽  
V. J. Schreiner ◽  
R. D. Readling
Keyword(s):  
Buccal Mucosa ◽  
Short Circuit ◽  
Basolateral Membrane ◽  
Electrical Potential ◽  
Short Circuit Current ◽  
Electrolyte Transport ◽  
Electrical Potential Difference ◽  
Ussing Chambers ◽  
Net Fluxes

The transmural electrical potential difference (PD) was measured in vivo across the buccal mucosa of humans and experimental animals. Mean PD was -31 +/- 2 mV in humans, -34 +/- 2 mV in dogs, -39 +/- 2 mV in rabbits, and -18 +/- 1 mV in hamsters. The mechanisms responsible for this PD were explored in Ussing chambers using dog buccal mucosa. After equilibration, mean PD was -16 +/- 2 mV, short-circuit current (Isc) was 15 +/- 1 microA/cm2, and resistance was 1,090 +/- 100 omega.cm2, the latter indicating an electrically "tight" tissue. Fluxes of [14C]mannitol, a marker of paracellular permeability, varied directly with tissue conductance. The net fluxes of 22Na and 36Cl were +0.21 +/- 0.05 and -0.04 +/- 0.02 mueq/h.cm2, respectively, but only the Na+ flux differed significantly from zero. Isc was reduced by luminal amiloride, serosal ouabain, or by reducing luminal Na+ below 20 mM. This indicated that the Isc was determined primarily by active Na+ absorption and that Na+ traverses the apical membrane at least partly through amiloride-sensitive channels and exits across the basolateral membrane through Na+-K+-ATPase activity. We conclude that buccal mucosa is capable of active electrolyte transport and that this capacity contributes to generation of the buccal PD in vivo.

Preclinical Safety and Pharmacology of an Anti-Human Interleukin-13 Monoclonal Antibody in Normal Macaques and in Macaques with Allergic Asthma

2008 ◽  
Vol 27 (5) ◽  
pp. 351-358 ◽  
Author(s):  
Pauline L. Martin ◽  
Dusti Fisher ◽  
William Glass ◽  
Karyn O’Neil ◽  
Anuk Das ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Allergic Asthma ◽  
Immunoglobulin E ◽  
Cynomolgus Macaque ◽  
Lavage Fluid ◽  
Antigen Challenge ◽  
Interleukin 13 ◽  
Lung Eosinophilia

Interleukin-13 (IL-13) plays a central role in chronic airway diseases, including asthma. These studies were conducted to evaluate the safety of administration of a human anti-IL-13 monoclonal antibody (mAb) to normal macaques and in macaques with allergic asthma. In addition, serum and bronchioalveolar lavage fluid were collected from allergic cynomolgus macaques in order to identify potential surrogate markers of IL-13 pharmacology that could be useful for subsequent clinical trials. In vitro studies demonstrated that the anti-IL-13 mAb inhibited the pharmacological actions of both human and cynomolgus macaque IL-13. Allergic macaques were treated systemically with 10 mg/kg anti-IL-13 mAb 1 day prior to inhaled Ascaris suum antigen challenge. Normal macaques were dosed intravenously with anti-IL-13 once per week for 3 weeks at doses of 10 or 50 mg/kg. Treatment of macaques with the anti-IL-13 mAb was not associated with any toxicologically significant findings. A slight treatment-related but nonadverse decrease in platelet counts was observed in both the normal and allergic macaques. In allergic macaques, the anti-IL-13 mAb treatment did not affect lung function, lung eosinophilia, or serum or BAL immunoglobulin E (IgE) concentrations but did produce a reduction in BAL and serum eotaxin concentrations ( p < .05) at 6 h post antigen challenge. This study shows that administration of an anti-IL-13 mAb was well tolerated in both normal and allergic asthmatic macaques and that serum eotaxin concentrations may be a useful early in vivo marker for evaluating IL-13 inhibition in patients with asthma.

Allergic Response

2019 ◽  
Author(s):  
Joud Hajjar ◽  
Lawrence B Schwartz
Keyword(s):  
Mast Cell ◽  
Immunoglobulin E ◽  
Signs And Symptoms ◽  
Specific Ige ◽  
Consensus Conference ◽  
Allergic Response ◽  
Working Definition ◽  
Keywords Allergy ◽  
Ige Mediated ◽  
Definition Of

The term hypersensitivity refers to diseases caused by an immune response, regardless of whether the response is against a pathogen, nonpathogen, or self and regardless of whether the response is directed by antibodies, lymphocytes, or innate pathways. The term anaphylaxis was coined in 1902 by Charles Richet, who received the Nobel Prize in 1913; this systemic allergic response is now known to be an immediate hypersensitivity reaction, initiated by allergen delivered to a host having allergen-specific IgE, thereby causing an IgE-mediated immunologic response and activating mast cells and basophils to secrete bioactive mediators. In 2005, the National Institutes of Health organized a consensus conference to develop a working definition of anaphylaxis, designed to be used by physicians at the bedside, as a serious allergic reaction that is rapid in onset, typically eliciting various combinations of cutaneous, cardiovascular, respiratory, and gastrointestinal manifestations, and may cause death.1,2 This facilitated the early treatment of such patients with epinephrine. Confusion arises over the misapplication of the term allergy or hypersensitivity to describe any untoward reaction to food, medications, or environmental exposures. Furthermore, non–IgE-mediated forms of local and systemic mast cell or basophil activation events can occur, causing signs and symptoms similar to those mediated by IgE.  This review contains 3 figures, 9 tables, and 62 references. Keywords: allergy, hypersensitivity, anaphylaxis, interleukin, chemokines, immunoglobulin E, mast cell, eosinophil

Mechanisms of sodium and chloride transport across equine tracheal epithelium

1990 ◽  
Vol 259 (6) ◽  
pp. L459-L467 ◽  
Author(s):  
G. J. Tessier ◽  
T. R. Traynor ◽  
M. S. Kannan ◽  
S. M. O3'Grady
Keyword(s):  
Chloride Transport ◽  
Short Circuit ◽  
Basolateral Membrane ◽  
Short Circuit Current ◽  
Ringer Solution ◽  
Tracheal Epithelium ◽  
Ussing Chambers ◽  
Cl Secretion ◽  
Cotransport System ◽  
Ethanesulfonic Acid

Equine tracheal epithelium, stripped of serosal muscle, mounted in Ussing chambers, and bathed in plasmalike Ringer solution generates a serosa-positive transepithelial potential of 10–22 mV and a short-circuit current (Isc) of 70–200 microA/cm2. Mucosal amiloride (10 microM) causes a 40–60% decrease in Isc and inhibits the net transepithelial Na flux by 95%. Substitution of Cl with gluconate resulted in a 30% decrease in basal Isc. Bicarbonate substitution with 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid decreased the Isc by 21%. The Cl-dependent Isc was inhibited by serosal addition of 1 mM amiloride. Bicarbonate replacement or serosal amiloride (1 mM) inhibits the net Cl flux by 72 and 69%, respectively. Bicarbonate replacement significantly reduces the effects of serosal amiloride (1 mM) on Isc, indicating its effect is HCO3 dependent. Addition of 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP; 100 microM) causes a 40% increase in Isc. This effect is inhibited by subsequent addition of 10 microM serosal bumetanide. Bumetanide (10 microM) reduces net Cl secretion following stimulation with 8-BrcAMP (100 microM). Serosal addition of BaCl2 (1 mM) causes a reduction in Isc equal to that following Cl replacement in the presence or absence of 100 microM cAMP. These results suggest that 1) Na absorption depends on amiloride-inhibitable Na channels in the apical membrane, 2) Cl influx across the basolateral membrane occurs by both a Na-H/Cl-HCO3 parallel exchange mechanism under basal conditions and by a bumetanide-sensitive Na-(K?)-Cl cotransport system under cAMP-stimulated conditions, and 3) basal and cAMP-stimulated Cl secretion depends on Ba-sensitive K channels in the basolateral membrane.

Short-chain fatty acids inhibit cAMP-mediated chloride secretion in rat colon

1996 ◽  
Vol 271 (6) ◽  
pp. C1853-C1860 ◽  
Author(s):  
P. C. Dagher ◽  
R. W. Egnor ◽  
A. Taglietta-Kohlbrecher ◽  
A. N. Charney
Keyword(s):  
Fatty Acids ◽  
Short Circuit ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Rat Colon ◽  
Sprague Dawley ◽  
T84 Cells ◽  
Ussing Chambers ◽  
Cl Secretion ◽  
Chain Fatty Acids

Butyrate stimulates salt absorption in mammalian colon. We examined whether butyrate also affects Cl- secretion. Mucosal segments of distal colon of male Sprague-Dawley rats and T84 cells were studied in Ussing chambers. In control colon, 1 mM dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) increased short-circuit current (Isc) and serosal-to-mucosal Cl- flux (JsmCl) by 3.2 +/- 0.8 and 2.9 +/- 0.8 mueq.cm-2.h-1, respectively. Mucosal or serosal 25 mM butyrate prevented DBcAMP-induced increases in Isc and JsmCl. Four and eight millimolar butyrate caused half-maximal inhibition of the increases in JsmCl and Isc, respectively. Butyrate also inhibited basal JsmCl (by 2.0 +/- 0.4 mueq.cm-2.h-1) but not carbachol-mediated Cl- secretion. The relative inhibitory potency at 25 mM of other short-chain fatty acids (SCFA) paralleled their degree of cellular metabolism: butyrate > acetate = propionate > isobutyrate. At 25 mM, all SCFA reduced mucosal intracellular pH (pHi) transiently by 0.1 pH unit. In intact T84 cells, 50 mM butyrate inhibited the DBcAMP-induced rise in Isc by 55%. In T84 cells with nystatin-permeabilized basolateral membranes, butyrate inhibited the increase in Isc by 82%. We conclude that butyrate inhibits basal and cAMP-mediated Cl- secretion by a mechanism independent of pHi, possibly located at the apical membrane.

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