The cost of our good intentions.
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Critical Care↗
Biomedical subjects
A R Leff
Publications and source records attributed to A R Leff.
New method for real-time measurements of changes in lumenal area of microsection explants of airways by videomicrometry.
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Acetylcholine↗
Cyproheptadine-induced attenuation of type-I immediate-hypersensitivity reactions of airway smooth muscle from immune-sensitized cats.
We assessed the effect of serotonergic inhibition by cyproheptadine on the responsiveness of tracheal smooth muscle (TSM) strips and epithelium-intact third-generation bronchial rings from immune-sensitized (Ascaris suum) cats after exposure to antigen. Cats were sensitized by IM administration of antigen and adjuvant twice over a 4-week period. Sensitization was confirmed in vivo by skin testing with antigen and by physiologic airway responses after exposure to nebulized antigen. Tissues were tethered isometrically to force transducers and were actively equilibrated by exposures to KCl-substituted perfusate. Maximal response after exposure to antigen (expressed as percentage of maximal contraction of each tissue to 63 mM KCl (%KCl) was 169 +/- 18% KCl for sensitized TSM and 43 +/- 18% KCl for sensitized TSM pretreated with cyproheptadine (P < 0.001). Similarly, maximal response to antigen was 81 +/- 27% KCl for sensitized bronchial rings, compared with 16 +/- 14% KCl for sensitized bronchial rings pretreated with cyproheptadine (P = 0.05 vs control). Blockade of leukotriene synthesis by 10(-6) to 10(-4) M A-64077, a selective 5-lipoxygenase inhibitor, had no significant effect on peak response for either TSM (193 +/- 13% KCl vs 169 +/- 18% KCl for sensitized untreated TSM) or bronchial rings (79 +/- 20% KCl vs 81 +/- 27% KCl for sensitized untreated bronchial rings). Release of serotonin from airway tissues was confirmed by the presence of serotonin in the perfusate of 8 sensitized TSM preparations after, but not before, antigen challenge.(ABSTRACT TRUNCATED AT 250 WORDS)
Airway Resistance↗
Paradoxical blockade of beta adrenergically mediated inhibition of stimulated eosinophil secretion by salmeterol.
Salmeterol (SALM) is a long-acting beta 2 adrenoceptor agonist that causes prolonged relaxation of airway smooth muscle. To determine whether this agent also causes prolonged inhibition of stimulated eosinophil secretion, we studied interactions between SALM and albuterol (ALB) in inhibiting eosinophil peroxidase (EPO) secretion in human eosinophils in vitro. Peripheral blood eosinophils were isolated from 18 human volunteers by negative immunoselection, and secretion of EPO was elicited with 10(-6) M formyl-met-leu-phe (fMLP) + 5 micrograms/ml cytochalasin B (CytB) in aliquots of 10(5) cells. Eosinophils were pretreated with either 10(-8) M ALB, 10(-8) M SALM or SALM + ALB for 5 min to 18 hr at 37 degrees C. Pretreatment with ALB for 5 min caused inhibition of stimulated secretion of EPO to 783 +/- 210 ng/10(6) cells vs. 1475 +/- 286 ng/10(6) cells for eosinophils not treated with ALB (P < .05; n = 5). Inhibition of EPO secretion caused by ALB was sustained for 30 min (924 +/- 160 ng/10(6) cells; P < .05 vs. fMLP + CytB; n = 5). By contrast, SALM had no inhibitory effect on fMLP-induced secretion after incubation for 5 min to 18 hr. In cells obtained from four separate isolations, pretreatment with 10(-8)M SALM before addition of ALB blocked the inhibition of EPO release caused by 10(-8)M ALB alone (486 +/- 28 ng/10(6) cells for ALB alone vs. 902 +/- 32 ng/10(6) cells for SALM + ALB; P < .01; n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-Agonists↗
Immune sensitization augments epithelium-dependent spontaneous tone in guinea pig trachealis.
We examined epithelial modulation of tracheal smooth muscle (TSM) responsiveness in vitro from guinea pigs receiving active immune sensitization in vivo. Initially, guinea pigs were either ovalbumin sensitized (by aerosol) or sham sensitized with normal saline; TSM responsiveness was assessed isometrically as active tension (AT) after equilibration by electrical field stimulation in vitro. For epithelium-intact (Epi+) tissues, sensitization caused an increase in baseline active spontaneous tone (1.89 +/- 0.20 g AT) vs. sham-sensitized tissues (1.18 +/- 0.28 g AT; P = 0.02). Spontaneous tone in sensitized TSM in which the epithelium was removed (Epi-) (1.01 +/- 0.14 g AT) was substantially less than from Epi+ tissues (P = 0.01) and did not differ from sham-sensitized epithelium-denuded tissues (0.82 +/- 0.24 g AT; P > 0.05). Indomethacin caused a reduction in spontaneous tone to comparable magnitude for all treatment paradigms. Immune sensitization caused physiological reduction in the ability to relax in response to isoproterenol; the concentration of isoproterenol eliciting 50% relaxation of spontaneous tone was 7.10 +/- 0.13 (-log M) for TSM from sensitized guinea pigs compared with 8.20 +/- 0.27 (-log M) for sham-sensitized tissues (P = 0.006). However, after precontraction with exogenous acetylcholine, relaxation caused by isoproterenol was not affected by either indomethacin or epithelial removal. Muscarinic responsiveness to acetylcholine was augmented by immune sensitization; however, the increase in response to acetylcholine was attenuated by epithelium removal or cyclooxygenase blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylcholine↗
Passive sensitization of human bronchi augments smooth muscle shortening velocity and capacity.
We assessed whether incubation with human serum from atopic individuals containing high concentrations of immunoglobulin E (IgE) causes augmentation of maximal contraction of human bronchial smooth muscle from non-atopic subjects in vitro. Bronchi were obtained from eight patients undergoing lung resection, and force-velocity relationships were determined for eight pairs of epithelium-intact bronchial rings of generations 6-7 using an electromagnetic lever system, which allowed isotonic shortening when load-clamps [from 0 to maximal isometric force (P0)] were applied at specific times after onset of contraction. Contractions were elicited by supramaximal electrical field stimulation (50 Hz, 10 s train duration, 25 V). Optimal length (Lo) for each tissue was determined during equilibration. After resection, tissues were sensitized passively with human sera containing high titers (> 1,000 U/ml) of IgE by incubation for 16 h at 20 degrees C. Maximal shortening velocity (Vmax) was increased for passively sensitized bronchi [0.1150 +/- 0.0240 1/2 circumferences/s (1/2Cir/s)] compared with sham-sensitized bronchi [0.0731 +/- 0.0152 1/2Cir/s, P = 0.038]. Similarly, maximal shortening (delta Lmax) was augmented in sensitized bronchial rings (11.27 +/- 1.80 %Lo) compared with sham-sensitized tissues (8.19 +/- 1.39 %Lo, P = 0.012). However, P0 did not differ between sensitized (122.5 +/- 24.4 mN/cm2) compared with sham-sensitized tissues (138.4 +/- 32.1 mN/cm2, P = 0.642). Our data are the first demonstration that Vmax and delta Lmax are augmented in sensitized but not challenged human bronchial rings after passive sensitization using human serum containing high concentrations of IgE.
Bronchi↗
Contraction of human bronchial smooth muscle caused by activated human eosinophils.
We assessed the effect of activated eosinophils isolated from human peripheral blood in causing contraction of explanted human bronchi in vitro. Sixty-three epithelium-intact fifth generation airway sections were obtained from 16 subjects undergoing lung resection for carcinoma. Eosinophils were isolated by negative immunoselection, and activation with 10(-7) M platelet-activating factor (PAF) was confirmed by measurements of eosinophil peroxidase (EPO) secretion and superoxide (O2-.) generation. EPO secretion increased from 68.6 +/- 13.4 ng/10(6) cells to 420 +/- 125 ng/10(6) cells after activation with PAF (P < 0.05). Similarly, PAF-induced O2-. generation increased from 15.3 +/- 4.64 nmol cytochrome c reduced/10(5) cells to 44.2 +/- 8.50 nmol cytochrome c reduced/10(5) cells (P < 0.05). Cells were instilled into an isolated airway pouch preparation, and, 60 min later, airway contractile responses were determined by optical micrometry as percent decrease in lumenal diameter (%decrease) and percent increase in wall thickness (%increase) using a calibrated magnifying lens. Treatment with either vehicle, PAF alone, or untreated eosinophils had no effect on airway caliber or thickness. PAF-activated cells caused a 30.5 +/- 1.52% decrease in airway caliber (P < 0.001 vs. untreated cells) and a 36.6 +/- 2.54% increase in wall thickness (P < 0.001 vs. untreated cells). Preincubation with A63162, a 5-lipoxygenase inhibitor, caused concentration-dependent inhibition of airway narrowing. After 10(-5) M A63162, decrease in airway diameter caused by PAF was 8.00 +/- 0.10% vs. 30.5 +/- 1.52% for PAF alone (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Acetamides↗
Ontogeny of dry gas hyperpnea-induced bronchoconstriction in guinea pigs.
Adolescent guinea pigs (AGPs) demonstrate dry gas hyperpnea-induced bronchoconstriction (HIB) that shares key features with HIB in humans with asthma. The airways of immature animals exhibit enhanced reactivity to diverse types of stimulation. We tested whether dry gas HIB is also increased in newborn guinea pigs (NGPs). We quantified HIB as the fractional increase of respiratory system resistance (Rrs) over baseline (BL) in five 4- to 7-day-old NGPs after 10 min of hyperpnea, as well as changes in Rrs elicited by intravenous methacholine or capsaicin, and compared these responses with those of AGPs. During hyperpnea, analogous stimuli were delivered by mechanically imposing hyperpnea at 3.0, 4.5, and 6.0 times quiet eucapnic minute ventilation (VE). In AGPs, hyperpnea caused significant bronchoconstriction that increased with VE; peak fractional increase of Rrs was 7.6 +/- 2.0 times BL. In contrast, hyperpnea caused insignificant bronchoconstriction in NGPs (1.4 +/- 0.2 times BL after the largest VE; P < 0.05 vs. AGP). Responses elicited by methacholine (10(-10)-10(-7) mol/kg) or capsaicin (0.01-10.0 microgram/kg) were similar in NGPs and AGPs. In AGPs, hyperpnea suppressed HIB until posthyperpnea. To determine whether the reduced HIB of NGPs was caused by enhanced suppression, NGPs and AGPs were administered acetylcholine (10(-10)-10(-7) mol/kg i.v.) during BL eucapnic ventilation and during eucapnic hyperpnea with warm humidified gas. Responses to acetylcholine were suppressed in AGPs and NGPs to a similar degree. We conclude that HIB is markedly diminished shortly after birth in guinea pigs and that it increases substantially during maturation.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylcholine↗
Migration of human and guinea pig airway epithelial cells in response to calcitonin gene-related peptide.
Calcitonin gene-related peptide (CGRP) is contained within and secreted by nerves and neuroepithelial bodies in the airway epithelium. To determine whether CGRP is a chemoattractant, tracheal epithelial cells isolated from 23 guinea pigs, and bronchial epithelial cells isolated from seven human donors were grown in primary culture for 4 to 5 days. Cell migration was assessed in a blindwell chemotaxis chamber. A gelatin-coated polycarbonate filter (8-microns pore size) separated the upper wells containing 5 x 10(4) cells from the lower wells containing chemoattractant (either CGRP or insulin). Cells were stimulated for 6 h, after which migrated cells on the filter were stained and counted. Both insulin and CGRP elicited migration of guinea pig tracheal epithelial (GPTE) cells. Exposure to 30 micrograms/ml insulin caused migration of 26.5 +/- 4.0 cells versus 4.3 +/- 0.6 cells per 10 hpf for control (P < 0.001). Treatment with 10(-9) M CGRP elicited migration of 39.6 +/- 2.5 cells versus 2.6 +/- 0.9 cells per 10 hpf for control (P < 0.001). Human bronchial epithelial (HBE) cells also migrated after stimulation with either insulin or CGRP: after 10(-9) M CGRP, HBE cell migration was 41.0 +/- 6.1 cells versus 3.4 +/- 0.3 cells per 10 hpf (P < 0.002; n = 3). Checkerboard analysis showed that the migration to CGRP was both chemotactic and chemokinetic. Incubation with 10(-8) M hCGRP-(8-37), a receptor antagonist for CGRP, plus 10(-9) M CGRP decreased GPTE cell migration to 9.8 +/- 2.4 cells versus 38.6 +/- 1.2 cells per 10 hpf for 10(-9) M CGRP alone (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Augmentation of stimulated eosinophil degranulation by VLA-4 (CD49d)-mediated adhesion to fibronectin.
We examined the effect of VLA-4-mediated adhesion to purified fibronectin (FN) on the stimulated release of the granular protein, eosinophil peroxidase (EPO), in human peripheral blood eosinophils. In initial studies, optimal time-course and concentration-effect relationships were determined; eosinophil adhesion to FN-coated styrene plates was maximal in wells coated with 10 micrograms/ml FN after incubation in the wells for 60 min (17,097 +/- 3,670 adherent eosinophils/well versus 6,789 +/- 925 adherent eosinophils/well in control wells; P < 0.005). Treatment of eosinophils with 10(-8) to 10(-6) M formylmethionylleucyl-phenylalanine (FMLP) + 5 micrograms/ml cytochalasin B (CYTB) caused a concentration-dependent increase in EPO release, which was augmented by preincubation of eosinophils for 120 min in FN-coated (10 micrograms/ml) styrene wells versus eosinophils preincubated in control wells. At 10(-6) M FMLP+CYTB, initial adhesion to FN for 120 min caused an increase in the secretion of EPO from 367 +/- 26 to 485 +/- 25 ng/10(6) eosinophils (P = 0.0001). Treatment of eosinophils during incubation in FN-coated wells with the anti-VLA-4 monoclonal antibody HP2/1 attenuated stimulated EPO secretion caused by 10(-6) M FMLP+CYTB from 497 +/- 40 to 285 +/- 26 ng/10(6) eosinophils (P < 0.02). Similarly, treatment with HP2/1 caused a decrease in eosinophil adhesion to FN-coated styrene from 12,693 +/- 1,866 to 6,206 +/- 852 adherent cells/FN-coated well (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Antibodies, Monoclonal↗
Inflammatory mediation of airway hyperresponsiveness by peripheral blood granulocytes. The case for the eosinophil.
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Animals↗
Beta adrenergic modulation of formyl-methionine-leucine-phenylalanine-stimulated secretion of eosinophil peroxidase and leukotriene C4.
The inhibitory effect of beta-2 adrenergic receptor stimulation on leukotriene C4 (LTC4) secretion and eosinophil peroxidase (EPO) release caused by exogenous activation with 10(-8) to 10(-6) M formyl-met-leu-phe (fMLP) + 5 micrograms/ml of cytochalasin B (Cyto B) in purified human peripheral blood eosinophils was studied. Cells from normal subjects were isolated by negative immunoselection and remained > or = 98% viable as determined by trypan blue exclusion. Duplicate aliquots of eosinophils (10(5) cells/intervention) were activated with 1) fMLP + Cyto B alone, 2) fMLP + Cyto B after pretreatment with 10(-8) M albuterol, 3) 10(-8) M albuterol + fMLP + Cyto B after pretreatment with 10(-8) M propranolol or 4) vehicle control. After incubation, the supernatants were tested for concentration of LTC4 and EPO. Concentration-related release of EPO was demonstrated for 10(-8) M fMLP + 5 micrograms/ml of Cyto B to 10(-6) M fMLP + 5 micrograms/ml of Cyto B, and the greatest concentration of fMLP was used in all subsequent studies. FMLP + Cyto B caused substantial LTC4 secretion in eosinophils (300 +/- 83.0 pg/ml) as compared to sham-activated eosinophils (3.3 +/- 1.9 pg/ml; P < .02). Similarly, maximum EPO release increased from 277 +/- 17.8 to 3956 +/- 1230 ng/10(6) cells (P < .02) after activation with fMLP + Cyto B. Treatment with albuterol decreased markedly both LTC4 secretion to 144 +/- 54.0 pg/ml (P < .05 vs. fMLP + Cyto B-activated eosinophils) and EPO release to 1993 +/- 368 ng/10(6) cells (P < .05 vs. fMLP + Cyto B-activated eosinophils).(ABSTRACT TRUNCATED AT 250 WORDS)
Albuterol↗
Sequence and functional characterization of feline interleukin 2.
Since the discovery of its involvement in the pathogenesis of feline immunodeficiency virus infection ("cat AIDS") and feline leukemia virus infection, the role of feline interleukin 2 (IL-2) has been a focus of particular interest. The purpose of this study was to clone feline IL-2 cDNA, as well as synthesize bioactive recombinant feline IL-2. The isolation of cDNA encoding feline IL-2 was carried out using a PCR-based strategy and screening of a feline leukocyte cDNA library. Feline IL-2 consists of 154 amino acids including a putative signal sequence and has 81%, 69%, 60% and 64% identity to human, bovine, murine and rat IL-2, respectively. Feline IL-2 cDNA was expressed in COS-7 cells. The secreted protein has CTLL-4 murine cytotoxic T cell proliferative activity characteristic of authentic IL-2. These data confirm the synthesis of bioactive recombinant feline IL-2.
Amino Acid Sequence↗
Activation of tracheal smooth muscle responsiveness by fMLP-treated HL-60 cells and neutrophils.
We assessed the effects of cultured human promyelocytic leukemia (HL-60) cells and polymorphonuclear leukocytes (neutrophils) isolated from peripheral human blood on tracheal smooth muscle responsiveness in 40 male Hartley guinea pigs. Undifferentiated HL-60 cells (16-25 passages) were activated in vitro by incubation with 1 microM f-Met-Leu-Phe (fMLP), and force of contraction was measured isometrically using an in situ preparation of tracheal smooth muscle. Increasing concentrations of acetylcholine (ACh; 10(-10) to 10(-6) mol/cm2 tracheal surface) were applied topically to the epithelial surface pretreated with 4 x 10(6) fMLP-activated HL-60 cells, 4 x 10(6) fMLP-activated neutrophils, 4 x 10(6) sham-activated HL-60 cells, fMLP+vehicle, or vehicle control. Topical application of fMLP-activated HL-60 cells caused a maximum active tension (AT) of 1.13 +/- 0.2 g/cm after 5 min; fMLP-activated neutrophils, sham-activated HL-60 cells, or fMLP+vehicle had no effect. The fMLP-activated HL-60 cells also caused substantial augmentation of tracheal contraction to ACh (P < 0.05 vs. sham-activated cells for all concentrations > 10(-9) mol/cm2). Although fMLP treatment caused 247 +/- 28% increase from baseline level in O2-. production, neither direct contraction nor augmentation of muscarinic stimulation was demonstrated after topical application of 4 x 10(6) neutrophils. In 12 other preparations, fMLP-activated HL-60 cells were pretreated with either 10 microM indomethacin (Indo) or 100 microM A63162, a 5-lipoxygenase inhibitor. Pretreatment with Indo caused complete blockade of direct tracheal contraction and 88 +/- 13% blockade of muscarinic augmentation; there was no effect after A63162.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetamides↗
Effect of mode of activation of human eosinophils on tracheal smooth muscle contraction in guinea pigs.
We studied the relationship between mode of activation of isolated human eosinophils and in situ responsiveness in isolated tracheal smooth muscle (TSM) of guinea pigs. Human peripheral blood eosinophils were activated with either 10(-7) M phorbol myristate acetate (PMA) or 10(-6) M formyl-methionyl-leucyl-phenylalanine (fMLP) + 5 micrograms/ml cytochalasin B (CYB), and activation was confirmed by measurement of eosinophil peroxidase (EPO) secretion by kinetic assay. EPO secretion was similar after activation with fMLP+CYB (10.2 +/- 3.2% of total eosinophil content) and PMA (10.0 +/- 2.8% of total content; P = NS). Topical application of 6 x 10(6) eosinophils/cm2 activated with fMLP+CYB to the TSM segment caused 0.51 +/- 0.14 g/cm active tension (AT) in five preparations (P < 0.03 vs. baseline); cells activated with PMA caused no contractile response (0.04 +/- 0.03 g/cm AT, P = NS vs. baseline). Both PMA- and fMLP+CYB-activated cells caused augmentation of muscarinic responsiveness of guinea pig trachealis. The dose of intravenous acetylcholine required to cause a threshold response (ED0.3) was -7.3 +/- 0.1 log mol/kg at baseline vs. -8.7 +/- 0.5 log mol/kg after treatment with fMLP+CYB-activated eosinophils (P = 0.05) and -6.9 +/- 0.1 log mol/kg at baseline vs. -7.5 +/- 0.1 log mol/kg after PMA-activated cells (P < 0.01). Both AT and augmented muscarinic responsiveness were blocked by pretreating the eosinophils with 200 microM A-63162, an inhibitor of 5-lipoxygenase, before activation with fMLP+CYB. We demonstrate that eosinophils activated comparably (as assessed by EPO secretion) cause augmented muscarinic responsiveness and/or direct contraction of guinea pig TSM through secretion of a product of the 5-lipoxygenase pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetamides↗
Effect of immune sensitization on stimulated ACh release from trachealis muscle in vitro.
We assessed the effect of immune sensitization on acetylcholine (ACh) release from parasympathetic nerve terminals in tracheal smooth muscle (TSM) strips from ragweed-sensitized (RWS) and sham-sensitized, littermate control (LMC) dogs. Strips of TSM were tethered to force transducers at optimal length in perfusion chambers containing [3H]choline and a fixed volume of physiological perfusate. Tissues were equilibrated for 1 h by electrical field stimulation (EFS) every 5 min to facilitate uptake of label into parasympathetic nerves as ACh. Fresh perfusate (containing 3 x 10(-8) M physostigmine) was collected at 5-min intervals for 1 h, and a rate coefficient of [3H]ACh release was determined. Tissues were exposed to agonists in the seventh collection period, and the increase in label release (ratio change where < or = 1.00 = baseline) and force production were determined. Ragweed antigen challenge stimulated [3H]ACh release and contraction in RWS but not LMC tissues. [3H]ACh release was 1.93 +/- 0.22 x baseline in RWS vs. 0.92 +/- 0.02 in control tissues (P < 0.01); contraction was 31.2 +/- 9.5% of that elicited by EFS (% EFS) in RWS vs. 0% EFS in LMC tissues (P < 0.01). Strips of TSM from RWS but not LMC dogs demonstrated concentration-dependent, augmented release of ACh caused by histamine. After 10(-4) M histamine, [3H]ACh release in RWS was 1.94 +/- 0.37 x baseline vs. 1.05 +/- 0.06 for LMC tissues (P < 0.05); histamine also caused greater contraction in RWS (106.5 +/- 5.9% EFS) vs. LMC (86.5 +/- 5.6% EFS; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylcholine↗
Effects of activated eosinophils cultured from human umbilical cord blood on guinea pig trachealis.
We studied the biochemical indexes and corresponding induction of airway smooth muscle contraction and hyperresponsiveness in guinea pig trachealis in situ caused by cultured eosinophils derived from mononuclear cell fractions of human umbilical cord blood. A method was developed that permitted isolation of large numbers of cells (approximately 2.6 x 10(6)/ml cord blood) having morphological and immunohistological characteristics of human peripheral blood eosinophils. After activation with 10(-6) M formyl-Met-Leu-Phe + 5 micrograms/ml cytochalasin B (fMLP + B), in situ application to the epithelial surface of 6 x 10(6) cord-derived eosinophils (CDE)/surface area (cm2) caused 1.46 +/- 0.24 g/cm maximal active tracheal tension in guinea pig tracheal smooth muscle (P < 0.005 vs. zero baseline). Muscarinic responsiveness also was augmented in situ in trachealis preparations treated with activated 3-wk CDE. Contraction caused by 3 x 10(-7) mol/kg iv methacholine (MCh) was 0.94 +/- 0.18 g/cm at baseline vs. 1.80 +/- 0.24 g/cm after activated CDE (P = 0.02). Control (sham-activated) 3-wk CDE caused neither significant contraction [0.41 +/- 0.16 g/cm active tension (AT); P < 0.05 vs. fMLP+B] nor augmented muscarinic responsiveness. Cells cultured for 5 wk contained fewer granules than 3-wk CDE and also caused less direct contraction of trachealis (0.73 +/- 0.14 g/cm AT) after activation (P < 0.01 vs. 3-wk CDE). Both contraction and muscarinic augmentation were blocked in 3-wk CDE after blockade of leukotriene C4 (LTC4) synthesis by pretreatment with the 5-lipoxygenase inhibitor, A63162 (50 microM). Treatment with A63162 had no effect on the stimulated release of eosinophil peroxidase.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗