calcimycin and Lung-Diseases--Obstructive

How leukotrienes (LTs) and IgE-mediated allergy reflect clinical features in patients with chronic obstructive pulmonary disease (COPD) remains unclear.. Our goal was to determine whether LTB4 and LTC4 would correlate with airway obstruction and whether IgE-mediated allergy would influence the generation of LTs and bronchial hyperresponsiveness in patients with COPD.. We measured the pulmonary function, methacholine bronchial hyperresponsiveness, and generation of LTB4 and LTC4 from peripheral leukocytes stimulated with calcium ionophore A23187 in relation to the presence of specific IgE antibodies against inhalant allergens.. The leukocytes of patients with COPD generated significantly more LTB4 (with allergy, P <.001; without allergy, P <.001) and LTC4 (with allergy, P <.001; without allergy, P <.01) than the leukocytes of the control subjects. LTC4 production was significantly higher in the allergic COPD subjects than in the nonallergic COPD patients (P <.01), but the amount of LTB4 generated was not significantly different. FEV(1) significantly correlated with the level of both LTB4 (with allergy, r = -0.556, P =.0375; without allergy, r = -0.731, P =.0046) and LTC4 (with allergy, r = -0.764, P =.0043; without allergy, r = -0.526, P =.0414) generation in COPD. The log(10) of the minimum dose of methacholine was significantly higher in COPD patients without allergy than in those with allergy (P <.05).. Enhanced LT generation from peripheral leukocytes is observed in patients with COPD, and the presence of specific IgE antibodies against inhalant allergens enhances LTC4 generation, bronchial hyperresponsiveness, and the relationship between LTC4 generation and airway obstruction.

Topics: Antibodies, Anti-Idiotypic; Antibody Specificity; Bronchial Hyperreactivity; Calcimycin; Humans; Immunoglobulin E; Leukocytes; Leukotrienes; Lung Diseases, Obstructive; Respiratory Hypersensitivity

To determine the capacity of pulmonary mast cells (PMC) to degranulate in response to various potential allergens and other secretagogues in horses with recurrent airway obstruction (heaves) and clinically normal horses before and after exposure to moldy hay.. 5 horses with heaves and 5 clinically normal horses.. Heaves was characterized as an increased clinical respiratory score and maximum change in transpulmonary pressure of > 20 cm H2O after exposure. Bronchoalveolar lavage was performed during each period. Washed and resuspended cells were exposed for 20 minutes at 37 C with whole reconstituted freeze-dried preparations of Aspergillus fumigatus, Alternaria tenuis, and Ambrosia elatior, fungal extracts of Aspergillus fumigatus, Alternaria tenuis, and Micropolyspora faeni; A23187; and compound 48/80. Histamine release (HR) was used as a marker of degranulation.. Compared with clinically normal horses, HR was significantly greater from PMC from horses with heaves during remission and exacerbation in response to whole preparations and extracts of Aspergillus fumigatus and whole preparations of Alternaria tenuis. Extracts of Alternaria tenuis caused significantly greater HR from PMC from horses with heaves during exacerbation. Histamine was also released from PMC in response to A23187 and to changes in osmolality of the medium, but only as a result of cell lysis by compound 48/80.. Increased degranulation of PMC after antigenic challenge may contribute to the pathogenesis of heaves in horses.. Strategies for prevention and treatment that attenuate degranulation of PMC may assist in the clinical management of horses with heaves.

Topics: Airway Obstruction; Allergens; Alternaria; Animals; Aspergillus fumigatus; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Calcimycin; Cell Degranulation; Female; Fluorometry; Histamine; Histocytochemistry; Horse Diseases; Horses; Ionophores; Lung Diseases, Obstructive; Male; Mast Cells; Micromonosporaceae; p-Methoxy-N-methylphenethylamine; Respiratory Function Tests

1. Endothelium-dependent relaxation mediated by endothelium-derived relaxing factor (EDRF) or nitric oxide (NO), is impaired in pulmonary arteries (PA) of hypoxic patients with chronic obstructive lung disease (COLD). To determine the mechanisms responsible for this impairment, we compared the response of rings of isolated PA from 12 COLD patients and 8 controls to the endothelium-dependent vasodilators acetylcholine (ACh), adenosine diphosphate (ADP), and the calcium ionophore, A23187. The response of PA rings to the endothelium-independent nitro-vasodilator sodium nitroprusside (SNP) was also studied in both groups. The PA rings had been pre-contracted by the alpha-adrenoceptor agonist phenylephrine (PE). 2. Endothelium-dependent relaxation was significantly reduced in PA rings from COLD patients as compared with controls when tested with ACh (37.8 +/- 8.8% vs 73.4 +/- 7.9%), ADP (38.4 +/- 6.7% vs 80 +/- 5.6%), and the calcium ionophore, A23187 (35.8 +/- 6.1% vs 87 +/- 6.6%). Relaxation with SNP was, however, significantly greater in PA rings from COLD patients (99.4 +/- 0.6% vs 90.3 +/- 3.1%), as was the contractile response to PE (1.91 +/- 0.21 g vs 1.33 +/- 0.15 g). Pretreatment with the specific inhibitor of NO formation, NG-monomethyl-L-arginine (L-NMMA; 10(-4) M) significantly reduced the relaxation to ACh in all PA rings. This inhibition could be reversed by L-arginine (10(-3) M), the substrate for NO synthesis. Pretreatment with L-arginine alone, however, did not restore the impaired endothelium-dependent relaxation of PA rings from COLD patients. 3. We conclude that EDRF (NO) production is impaired in PA rings from COLD patients and that this impairment is neither due to endothelial receptors dysfunction nor a defect of L-arginine availability and/or transport. Our hypothesis is that the abnormality must lie within the biosynthesis pathway of NO from L-arginine, possibly involving the endothelial enzyme cell, NO synthase, the normal function of which might be altered by chronic hypoxia.

Topics: Acetylcholine; Adenosine Diphosphate; Adult; Aged; Amino Acid Oxidoreductases; Arginine; Blood Gas Analysis; Calcimycin; Cell Membrane; Endothelium, Vascular; Female; Humans; In Vitro Techniques; Lung Diseases, Obstructive; Male; Middle Aged; Muscle Relaxation; Muscle, Smooth, Vascular; Nitric Oxide Synthase; omega-N-Methylarginine; Pulmonary Artery; Respiratory Function Tests

A brief A23187 aerosol exposure produced prolonged airway obstruction with granulocyte accumulation in conscious guinea pigs. Aminophylline, atropine, pyrilamine, salbutamol, SC-41930 (a leukotriene B4 antagonist) and WEB 2086 (a platelet activating factor antagonist) were administered intravenously (i.v.) to evaluate their ability to prevent these changes. Inhaled salbutamol was also assessed. Aminophylline, atropine, and salbutamol (i.v. and aerosol) inhibited A23187-induced gas trapping (p less than 0.01). However, pyrilamine, SC-41930 and WEB 2086 did not influence this airway obstructive effect. Only atropine, inhaled salbutamol and SC-41930 inhibited the cell influx (p less than 0.01), while pyrilamine potentiated the inflammation (p less than 0.05). We conclude that A23187 produces a sustained bronchospasm and an intense granulocyte accumulation. The treatment agents tested differ considerably in their ability to alter A23187-induced airway obstruction and inflammation.

Topics: Albuterol; Aminophylline; Animals; Atropine; Bronchial Spasm; Calcimycin; Granulocytes; Guinea Pigs; Kinetics; Lung Diseases, Obstructive; Male; Pneumonia

Topics: Animals; Bronchi; Bronchitis; Calcimycin; Chromones; Female; Guinea Pigs; Humans; Ileum; In Vitro Techniques; Leukotrienes; Lung Diseases, Obstructive; Male; Mucous Membrane; Muscle Contraction; SRS-A