Azelastine and suplatast shorten the distribution half-life of IgE in rats

We aim to clarify whether suplatast and azelastine (anti-allergic drugs) can shorten the half-life of imnunoglobulin E (IgE) in the circulating blood. Thirty Wistar rats were divided into six groups. Distilled water or anti-allergic drugs were given orally for 6 days after the first sensitization. Two milligrams of monoclonal dinitrophenyl (DNP)-specific rat IgE was administered to the rats, which had been given suplatast or azelastine orally. The level of DNP-specific rat IgE in the serum was estimated by IgE-capture enzyme-linked immunosorbent assay, and the turnover of IgE was analyzed from its pharmacokinetic parameters. The elimination half-life of rat IgE was about 12 h irrespective of the sensitized state. The intercompartmental rate constants (Kct and Ktc) in the suplatast-administered or azelastine-administered group were larger than those of the distilled water-administered group under non-sensitized conditions. These findings suggested that the anti-allergic drugs used in the present study facilitated the excretion of IgE from the circulation in rats.     

Influence of hypoxia on the longitudinal distribution of pulmonary vascular resistance

We have examined the influence of hypoxia on the longitudinal distribution of vascular resistance and intravascular pressure in isolated cat lungs using the low-viscosity bolus technique. Hypoxia increased total vascular resistance, decreased total lung blood volume, and moved the maximum local resistance downstream away from the main pulmonary artery. The circumference of the main pulmonary artery was increased and the extravascular lung water (double indicator dilution technique) was decreased by hypoxia. Thus, it would appear that distension of the large pulmonary arteries and a decrease in the amount of lung tissue perfused contributed to the change in resistance distribution brought about by hypoxia.     

Purification,structural and immunological characterization of a timothy grass (Phleum pratense) pollen allergen,Phl p 4, with cross-reactive potential

Almost 500 million people worldwide suffer from Type I allergy, a genetically determined immunodisorder which is based on the production of IgE antibodies against per se harmless antigens (allergens). Due to their worldwide distribution and heavy pollen production, grasses represent a major allergen source for approximately 40% of allergic patients. We purified Phl p 4, a major timothy grass (Phleum pratense) pollen allergen with a molecular mass of 61.3 kDa and a pl of 9.6 to homogeneity. Circular dichroism spectroscopical analysis indicates that Phl p 4 contains a mixed alpha-helical/beta-pleated secondary structure and, unlike many other allergens, showed no reversible unfolding after thermal denaturation. We show that Phl p 4 is a major allergen which reacts with IgE antibodies of 75% of grass pollen allergic patients (n=150) and induces basophil histamine release as well as immediate type skin reactions in sensitized individuals. Phl p 4-specific IgE from three patients as well as two rabbit-anti Phl p 4 antisera cross-reacted with allergens present in pollen of trees, grasses, weeds as well as plant-derived food. Rabbit antibodies raised against Phl p 4 also inhibited the binding of allergic patients IgE to Phl p 4. Phl p 4 may thus be used for diagnosis and treatment of sensitized allergic patients.     

Airway hyperresponsiveness, late allergic response, and eosinophilia are reversed with mycobacterial antigens in ovalbumin-presensitized mice

Pretreatment with mycobacterial Ags has been shown to be effective in preventing allergic airway inflammation from occurring in a mouse model. Because most asthmatics are treated after the development of asthma, it is crucial to determine whether mycobacterial Ags can reverse established allergic airway inflammation in the presensitized state. Our hypothesis, based upon our previous findings, is that mycobacteria treatment in presensitized mice will suppress the allergic airway inflammation with associated clinical correlates of established asthma, with the noted exception of factors associated with the early allergic response (EAR). BALB/c mice sensitized and challenged with OVA were evaluated for pulmonary functions during both the EAR and late allergic response, and airway hyperresponsiveness to methacholine. Following this, sensitized mice were randomized and treated with placebo or a single dose (1 x 10(5) CFUs) of bacillus Calmette-Guérin (BCG) or Mycobacterium vaccae via nasal or peritoneal injection. One week later, the mice were rechallenged with OVA and methacholine, followed by bronchoalveolar lavage (BAL) and tissue collection. Mice treated with intranasal BCG were most significantly protected from the late allergic response (p < 0.02), airway hypersensitivity (p < 0.001) and hyperreactivity (p < 0.05) to methacholine, BAL (p < 0.05) and peribronchial (p < 0.01) eosinophilia, and BAL fluid IL-5 levels (p < 0.01) as compared with vehicle-treated, sensitized controls. Intranasal M. vaccae treatment was less effective, suppressing airway hypersensitivity (p < 0.01) and BAL eosinophilia (p < 0.05). No changes were observed in the EAR, BAL fluid IL-4 levels, or serum total and Ag-specific IgE. These data suggest that mycobacterial Ags (BCG>M. vaccae) are effective in attenuating allergic airway inflammation and associated changes in pulmonary functions in an allergen-presensitized state.     

Apparent volumes of distribution of 125-I-lothalamate and inulin in chickens.

The suitability of utilizing 125-I-iothalamate to estimate the volume of extracellular fluid was assessed in ureterally ligated chickens. Subsequent to intravenous administration the movement of labeled iothalamate from the plasma compartment follows closed two-compartment kinetics and equilibration between vascular and extravascular phases is attained in about 20 minutes. The volume of distribution of 125-I-iothalamate prior to and following the influsion of 0.15 M NaCl (equal to 15% of the estimated ECFV) averaged 23.6 plus or minus 0.61 and 28.4 plus or minus 0.22% of the body weight, respectively. The observed postsaline labeled iothalamate space did not differ statistically from the expected value. When administered simultaneously inulin penetrates into an apparent volume that is 75% of the labeled iothalamate space after 60 minutes. The content of 125-I-iothalamate is relatively high in liver and kidney tissue and suggests that these are major sites where removal of the indicator from plasma occur. It is suggested that 125-I-iothalamate, under appropriate conditions, could be used to measure the plasma volume and the extravascular fluid with which plasma is in rapid diffusion equilibrium.     

Albumin catabolism in diabetic rats

The kinetics of albumin catabolism were studied in normal rats and rats with streptozotocin induced diabetes (blood glucose greater than 500 mg%). Whether determined from the clearance of 125I-albumin from plasma or from the whole body, after 10 days of severe, uncontrolled diabetes there was a 30-35% decrease in the catabolic rate for albumin in the diabetic rats compared to normals. There was also about a 35% contraction of the relative extravascular distribution volume for albumin in the diabetic rats, and about a 25% decrease in the total body mass of albumin. However, the concentration of albumin in the circulation was the same in normal and diabetic animals. We conclude that when the rate of albumin synthesis is substantially depressed in diabetes, the rat maintains normal plasma albumin concentration both by decreasing albumin's fractional catabolic rate and by shifting albumin from the extravascular to the vascular compartment.     

Purification of adenylosuccinate lyase from rat skeletal muscle by a novel affinity column. Stabilization of the enzyme, and effects of anions and fluoro analogues of the substrate.

The turnover of prothrombin and of factor X was investigated in rabbits fed on a 1%-cholesterol-supplemented or a standard diet by studying the evolution of radioactivity in blood and in plasma from these animals after the intravenous injection of either 125I-rabbit factor X or 125I-bovine prothrombin. For factor X, half-lives and fractional pool sizes were similar for the two groups of rabbits in the extravascular, intravascular and plasma compartments. However, the equivalent plasma fractional pool size for the two groups of rabbits was only 73% of that in the intravascular compartment. The fractional catabolic rate for the hypercholesterolaemic rabbits [0.064 +/- 0.007 (of the intravascular pool)/h] was not significantly different from that in the rabbits fed on the standard diet (0.074 +/- 0.008/h). However, the absolute catabolic rate, and therefore the rate of synthesis, was significantly higher (1.261 +/- 0.141 mg/day per kg body wt. of rabbit) in the rabbits fed on the cholesterol-supplemented than that in the rabbits fed on the standard diet (0.705 +/- 0.019 mg/day per kg). The prothrombin half-lives and fractional pool sizes were similar for the two groups of rabbits in the extravascular and the intravascular compartments. The fractional catabolic rate for the hypercholesterolaemic rabbits [0.041 +/- 0.003 (of the plasma pool)/h] was not significantly different from that in the rabbits fed on the standard diet (0.035 +/- 0.003/h). However, the absolute catabolic rate and therefore the rate of prothrombin synthesis was significantly higher (3.96 +/- 0.48 mg/day per kg body wt.) in the rabbits fed on the cholesterol-supplemented than that in the rabbits fed on the standard diet (2.24 +/- 0.12 mg/day per kg).     

Concerted stimulation of PI-turnover, Ca2+-influx and histamine release in antigen-activated rat mast cells

Phospholipid metabolism in rat mast cells activated by antigen was examined with reference to phosphatidylinositol (PI) turnover. Upon antigen stimulation, histamine release from passively sensitized mast cells with IgE was potentiated by adding phosphatidylserine (PS). The addition of antigen to [3H]glycerol-prelabeled and sensitized mast cells induced a marked loss of radioactivity of PI and a concurrent accumulation of 1,2-diacylglycerol (DG) and phosphatidic acid (PA) within 5 to 60 sec. Furthermore, this antigen-induced PI breakdown was enhanced in the presence of Mg2+. Histamine release occurred in parallel with PI breakdown. On the other hand, the transient Ca2+ influx into mast cells, as measured by uptake of 45Ca2+, was found to occur quickly after cells were activated by antigen, which was concerted with PI breakdown. These results suggest that enhanced PI turnover may be an important step in the biochemical sequence of events leading to release of histamine, and that not only Ca2+ but also Mg2+ appears to take a part in stimulus-response coupling in rat mast cells.     

Regional extravascular density of the lung in patients with acute pulmonary edema

The regional distribution of extravascular lung density (lung tissue and interstitial or alveolar fluid per unit thoracic volume) and fractional pulmonary blood volume (volume of blood per unit thoracic volume) was measured in five patients with acute interstitial pulmonary edema and two patients with acute alveolar edema. We found a uniform increase in extravascular lung density in the patients with acute interstitial edema but a preferentially dependent distribution in the patients with alveolar edema. Fractional blood volume had an abnormally uniform distribution in patients with interstitial edema. In alveolar edema, there was marked redistribution of blood volume away from severely edematous regions. The results are in agreement with previous experimental work with animal models. The distribution of extravascular lung density and fractional blood volume in subjects with acute interstitial edema is, however, different from that found in subjects with chronic interstitial edema, suggesting that the pathophysiological characteristics of the two conditions may be different.     

IgE immune complexes stimulate an increase in lung mast cell progenitors in a mouse model of allergic airway inflammation

Mast cell numbers and allergen specific IgE are increased in the lungs of patients with allergic asthma and this can be reproduced in mouse models. The increased number of mast cells is likely due to recruitment of mast cell progenitors that mature in situ. We hypothesized that formation of IgE immune complexes in the lungs of sensitized mice increase the migration of mast cell progenitors to this organ. To study this, a model of allergic airway inflammation where mice were immunized with ovalbumin (OVA) in alum twice followed by three daily intranasal challenges of either OVA coupled to trinitrophenyl (TNP) alone or as immune complexes with IgE-anti-TNP, was used. Mast cell progenitors were quantified by a limiting dilution assay. IgE immune complex challenge of sensitized mice elicited three times more mast cell progenitors per lung than challenge with the same dose of antigen alone. This dose of antigen challenge alone did not increase the levels of mast cell progenitors compared to unchallenged mice. IgE immune complex challenge of sensitized mice also enhanced the frequency of mast cell progenitors per 10(6) mononuclear cells by 2.1-fold. The enhancement of lung mast cell progenitors by IgE immune complex challenge was lost in FcRγ deficient mice but not in CD23 deficient mice. Our data show that IgE immune complex challenge enhances the number of mast cell progenitors in the lung through activation of an Fc receptor associated with the FcRγ chain. This most likely takes place via activation of FcεRI, although activation via FcγRIV or a combination of the two receptors cannot be excluded. IgE immune complex-mediated enhancement of lung MCp numbers is a new reason to target IgE in therapies against allergic asthma.     

Application of on-chip cell cultures for the detection of allergic response

In this report, the development of a microfluidic cell chip for monitoring allergic response is described. A rat basophilic leukemia cell line (RBL-2H3), a tumor analog of rat mucosal mast cells, has been used as a model to observe its allergic response upon antigen stimulus. The cells were cultivated on a poly(dimethylsiloxane) (PDMS) chip, the surface of which was modified by several methods. The PDMS chip, which comprised a cell cultivation chamber and microfluidic channels, was fabricated by conventional molding methods. In order to detect the allergic response, a fluorescent dye, quinacrine, was introduced inside the cell compartment that included histamine. The cells were stimulated with dinitrophenylated bovine serum albumin (DNP-BSA) after incubation with anti-DNP IgE. When exocytosis events occurred, the microfluidic system detected the fluorescent signal of quinacrine, which was released from RBL-2H3 cells by using a photomultiplier tube (PMT) fitted onto a microscope.     

Rhythmic Variations of Pharmacokinetic Processes of Cyproterone Acetate in Rabbits

A study about the influence of administration time on pharmacokinetics of Cyproterone acetate in rabbits was performed. Thirty animals were distributed in six groups, each corresponding to a different time: 2, 6, 10, 14, 18 and 22 hours after light onset (HALO). Rabbits received a single intravenous administration of 4 mg kg^-1 Cyproterone acetate. Blood samples were taken and processed by high performance liquid chromatography. Plasmatic data were fitted to a biexponential equation. Concentration at zero time (Co), concentration at zero time extrapolated from the distribution phase (A), hybrid constant for distribution phase and its half life, volume of the central compartment (V_c), volume of distribution at steady state (V_ss), constants for transferring the drug from the central compartment to the exterior (K₁₀) and from the central to the peripheral compartment presented chronobiological variations (p < 0.05) and were fitted to a cosine equation. The following parameters adjusted to circadian rhythms: Co (Acrophase: 1.72 HALO); A (Acrophase: 4.09 HALO); V_c (Acrophase: 11.92 HALO); V_ss (Acrophase: 10.12 HALO) and K₁₀ (Acrophase: 3.59 HALO). It was concluded that pharmacokinetics of intravenously injected CPA in rabbits would behave in a different, though predictable, manner according to the animal's biological clock.     

The mechanism of reducing thiopentone dose in elderly patients undergoing surgery

The dose of thiopentone required to induce anesthesia in adults decreasing with age is not due to pharmacodynamic change. The change of pharmacokinetic properties of thiopentone with age in undergoing surgery patient's arterial blood was investigated in seven elderly (67-82 yr) and six young (21-33 yr) patients of both sexes. Thiopentone (3 mg kg-1) was administered intravenously and arterial blood samples were obtained immediately after the injection to measure plasma and red blood cell thiopentone concentrations by an HPLC method. Plasma protein binding was studied using ultracentrifuge method. The disappearance of thiopentone from the arterial blood was described by a two-compartment open model. The distribution rate constant (alpha) was significantly larger in the young patients (p less than 0.001). The distribution half-life was longer in the elderly (p less than 0.05). Both the input microscopic rate constant, K21, and the exit microscopic rate constant, K12, with the central compartment were significantly larger in the young patients. (p less than 0.02 and p less than 0.001, respectively). The difference between the exit and input microscopic rate constant, K12-K21, was much larger in the young patients (p less than 0.001). The plasma protein binding was significantly reduced in the elderly (p less than 0.05). The apparent overall volume of distribution, Vd was not significantly different between young and elder patients. However, the volume of distribution of the central compartment was smaller in the young patients (p less than 0.05). This was probably due to the difficulty of estimation of initial thiopentone plasma concentration post-equilibrium in the central compartment after administration of thiopentone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transvascular clearance and distribution of charged macromolecules in ANTU lung injury

Tissue uptake, extravascular distribution volumes, and plasma-lymph equilibration of two isozymes of lactate dehydrogenase (LDH) were labeled with radioiodine and studied in dogs with either normal or injured lungs. Cationic LDH 5 [isoelectric point (pI) = 7.9] was initially cleared from plasma by lung tissue at a rate 1.61 times higher (9.3 vs. 5.8 X 10(-3) ml X min-1 X g-1 extravascular wet wt) than anionic LDH 1 (pI = 5.0). LDH 5 also had a significantly higher extravascular distribution volume but equilibrated more slowly between plasma and pulmonary lymph (t1/2 = 120 min) than LDH 1 (t1/2 = 78 min) in normal lungs. Respective lymph-to-plasma ratios were 0.53 and 0.43 for LDH 1 and LDH 5 after 4 h of infusion. Infusion of the isozymes 2 h after injection of alpha-naphthylthiourea (ANTU) resulted in larger initial tissue plasma clearances for both isozymes compared with control, but greater relative tissue plasma clearances and extravascular distribution volumes for LDH 5 compared with LDH 1. Plasma-lymph equilibration half times of LDH 5 and LDH 1 were reduced after ANTU to 50 min and 41 min, respectively, whereas the respective alveolar fluid-to-plasma ratios of the two isozymes at termination of the ANTU experiments were 0.56 and 0.84. These data suggest that the fixed anionic charges on endothelial cell surfaces, intercellular junctions, basement membranes, and interstitial structures act much like a cation exchange gel to rapidly take up cationic proteins and retard the plasma-lymph equilibration of these proteins relative to anionic proteins of the same size.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of changes in intravascular oncotic pressure on renal responses to volume loading in the saltwater-acclimated Pekin duck (Anas platyrhynchos)

Summary The relative contributions of the intra-and extravascular compartments of the extracellular fluid (ECF) to the control of osmoregulatory renal functions were examined in saltwater-acclimated Pekin ducks. Having established steady-state diuresis and salt gland secretion by continuous infusion of 1 ml·min^-1 isotonic Krebs-Ringer-Bicarbonate (KRB) solution, 5% dextran-70 was added to the infusate for 30 min thereby confining volume expansion to the intravascular compartment. General volume expansion by isotonic KRB caused a drop in plasma osmolality by 23 mOsm·kg^-1, due to NaCl elimination by the salt glands, and decreases in hematocrit (het) and radioimmunologically measured plasma levels of Arg⁸-vasotocin (AVT) and Val⁵-angiotensin II (ANG II), whereas immunoreactivity associated with atrial natriuretic factor (ir-ANF) was increased. Adding 5% dextran-70 to the infusate left plasma osmolality and electrolytes unchanged but was followed by a further decrease in hct and a 36% increase in the plasma colloidosmotic pressure (COP) facilitating fluid shifts from the extra-to the intravascular compartment of the ECF. Plasma levels of AVT and ANG II remained unchanged, but ir-ANF rose three-fold, its increase being three times as great relative to the decrease in hct, as during general volume expansion by isotonic KRB solution. Arterial and central venous pressure measurements did not indicate changes in cardiovascular function. Hyperoncotic infusion initially induced marked antidiuresis with decreased osmolal excretion, despite a slightly elevated urine osmolality. This effects, however, was trasient and not proportional to the rise in COP, but rather seemed to be related to fluid shifts resulting from hyperoncotic loading. With tracer dilution techniques, reductions in both renal plasma flow and glomerular filtration rate were found to contribute to antidiuresis which was associated with reduced fractional water excretion. Salt gland secretion rate did not increase during hyperoncotic intravascular volume expansion but rather tended to decrease. The results of this study are in line with the idea that contributions of the interstitial fluid compartment (IFC) to volume-dependent control of osmoregulatory functions have to be considered. In the present study on saltwater-acclimated ducks, AVT, ANG II, and ir-ANF could be excluded as mediators of the adjustments in renal water and salt handling following fluid shifts due to hyperoncotic intravascular volume expansion.Abbreviations ANF atrial natriuretic factor - ir-ANF ANF-like immunoreactivity - ANG II angiotensin II - AVT arginine vasotocin - BF breathing frequency - b. w. body weight - COP colloid osmotic pressure - CVP central venous pressure - ECF extracellular fluid - ERPF effective renal plasma flow - FF filtration fraction - GFR glomerular filtration rate - IFC interstitial fluid compartment - i.v. intravenous(ly) - hct hematocrit - HR heart rate - KRB Krebs-Ringer Bicarbonate solution - MABP mean arterial blood pressure - PAH paraaminohippuric acid - SEM standard error of mean     

盐城地区未成年过敏性疾病患者吸入性过敏原IgE检测结果分析

摘要 目的：通过研究分析盐城地区未成年过敏性疾病患者吸入性过敏原特异性IgE检测结果分布变化特点,为过敏性疾病预防和临床诊疗提供科学依据。方法：自2020年1月至2021年3月期间,选择430例未成年(<18岁)过敏性疾病患者,血清检测方法采用欧蒙公司生产的过敏原特异性IgE检测试剂盒。结果：430例患者中,血清过敏原IgE阳性166例(38.60%),其中尘螨和屋尘是主要的吸入性过敏原。血清IgE阳性率男性39%,女性36% (P>0.05),中学组女性阳性率（61.11 %）高于男性（45.83 %）（P<0.05）。不同年龄组间IgE阳性率有统计学差异（P<0.05）,蟑螂、尘螨、霉菌、豚草、屋尘和年龄组间有统计学差异（P<0.05）。不同临床症状与IgE阳性率有统计学差异(P<0.05),其中呼吸道过敏症状组IgE阳性率最高（48.30 %）,不同症状组间主要过敏原都是尘螨。屋尘阳性患者均合并尘螨阳性,其中70.93 %的患者表现出了呼吸道过敏症状。结论：尘螨、屋尘是盐城地区未成年过敏性疾病患者最主要的吸入性过敏原,研究血清过敏原分布,对未成年人过敏性疾病的预防、诊疗具有重要意义。     

Effect of exercise and thermal stress on plasma volume.

Six male subjects exercised for 50 min at 25% (light exercise) and 55% (moderate exercise) of their estimated aerobic capacities in environments of 42 degrees C db, 35 degrees C wb and 30 degrees C db, 24 degrees C wb, respectively. Alterations in the hematocrit, hemoglobin, and plasma protein concentrations, and in the activity of an injected aliquot of isotopically labeled albumin were each used to calculate the percentage change in plasma volume occurring during exercise and recovery. Changes in each measure were consistent with a reduction in plasma volume during exercise and a return to preexercise levels during recovery. There was no significant difference between the measures when exercising in the heat, but during the more severe exercise in the cooler environment disproportional changes in protein, hematocrit, and hemoglobin were observed. Disproportional changes were also seen during the recovery phase, when the hematocrit and hemoglobin concentration indicated a more rapid return of the plasma volume to preexercise levels than did either the plasma protein concentration or albumin activity. During moderate exercise and recovery there was a 1% decrease in red cell volume. It is concluded that exercise accelerates the rate of protein movement from extravascular compartments to the intravascular compartment, leading to elevated plasma protein levels during recovery which favor the return of water to the intravascular space. Hemoglobin concentration is considered to be the most reliable measure of plasma volume change during exercise.     

Molecular, immunological, and structural characterization of Phl p 6, a major allergen and P-particle-associated protein from Timothy grass (Phleum pratense) pollen.

Due to the wide distribution and heavy pollen production of grasses, approximately 50% of allergic patients are sensitized against grass pollen allergens. cDNAs coding for two isoforms and four fragments of a major timothy grass (Phleum pratense) pollen allergen, Phl p 6, were isolated by IgE immunoscreening from a pollen expression cDNA library. Recombinant Phl p 6 (rPhl p 6), an acidic protein of 11.8 kDa, was purified to homogeneity as assessed by mass spectrometry and exhibited almost exclusive alpha-helical secondary structure as determined by circular dichroism spectroscopy. Phl p 6 reacted with serum IgE from 75% of grass pollen-allergic patients (n = 171). IgE binding experiments with rPhl p 6 fragments indicated that the N terminus of the allergen is required for IgE recognition. Purified rPhl p 6 elicited dose-dependent basophil histamine release and immediate type skin reactions in patients allergic to grass pollen. A rabbit antiserum raised against purified rPhl p 6 identified it as a pollen-specific protein that, by immunogold electron microscopy, was localized on the polysaccharide-containing wall-precursor bodies (P-particles). The association of Phl p 6 with P-particles may facilitate its intrusion into the deeper airways and thus be responsible for the high prevalence of IgE recognition of Phl p 6. Recombinant native-like Phl p 6 can be used for in vitro as well as in vivo diagnoses of grass pollen allergy, whereas N-terminal deletion mutants with reduced IgE binding capacity may represent candidates for immunotherapy of grass pollen allergy with a low risk of anaphylactic side effects.     

Role for IgE in airway secretions: IgE immune complexes are more potent inducers than antigen alone of airway inflammation in a murine model

IgE is present in airway secretions from human patients with allergic rhinitis and bronchial asthma. However, the contribution of IgE present locally to the overall airway inflammation is not well understood. We hypothesize that Ag-specific IgE can capture airborne Ags and form immune complexes. These immune complexes may function as potent inducers of immune responses in the lung, contributing to the perpetuation of airway inflammation. BALB/c mice were first sensitized with OVA in alum systemically and then challenged with nebulized OVA. Bronchoalveolar lavage (BAL) fluid from these mice contained significant amounts of IgE, of which >50% was Ag specific. The IgE levels in airway secretions remained elevated for more than 15 days after the termination of Ag exposure. Significant amounts of IgE-OVA immune complexes were detected in BAL fluid from the OVA-challenged mice. For comparison of IgE immune complexes vs Ag alone, we treated OVA-immunized mice with intranasal administration of trinitrophenyl-OVA or trinitrophenyl-OVA-anti-DNP IgE. Those treated with the immune complexes showed significantly higher levels of IL-4 and more pronounced eosinophilia in BAL fluid than did those receiving the Ag alone. The IgE immune complexes did not augment the inflammatory response in high affinity IgE receptor (FcepsilonRI)-deficient mice. We conclude that IgE present in the airways can capture the Ag and that the immune complexes thus formed may augment allergic airway response in an FcepsilonRI-dependent manner. Thus, IgE present in airway secretions may facilitate Ag-mediated allergic airway inflammation.     

Regional lung water and hematocrit determined by positron emission tomography

We have measured with positron emission tomography (PET) the regional distribution of extravascular lung water (EVLW) and hematocrit (HctL) in normal supine dogs. H2(15)O and C15O were used as total lung water (TLW) and intravascular water (IVW) compartment labels, respectively. An additional plasma volume label (68Ga-transferrin) was used to determine regional HctL. EVLW was calculated as the difference between TLW and IVW. In 13 dogs, EVLW was relatively constant along a gravity-dependent vertical gradient, although values in the most anterior regions were statistically less (P less than 0.05) than those in more posterior ones. The average value for EVLW (13 dogs) was 14.4 +/- 2.5 ml H2O/100 ml lung. When EVLW was compared with IVW on a regional basis, the EVLW/IVW ratio decreased significantly in a gravity-dependent direction from 1.95 +/- 0.28 to 0.88 +/- 0.18. In 7 dogs, no significant difference between HctL and systemic hematocrit (average ratio 1.01 +/- 0.08) was found nor was any significant variation of HctL within the lung detected. Thus, in contrast to gravimetric techniques, a hematocrit correction does not appear to be necessary when regional EVLW is studied by PET.