leukotriene-b4 and Alveolitis--Extrinsic-Allergic

In the present study we investigated the involvement of lipid mediators in an experimental model of immune-complex alveolitis induced in rat lungs by intrabronchial instillation of rabbit antibodies to ovalbumin followed by i.v. injection of the antigen. It was found that the reaction did not induce detectable oedema, as measured by the dry:wet weight ratio. A marked influx of neutrophils was observed in the bronchoalveolar lavage fluid, progressing from 6 to 24 h in parallel with the development of haemorrhagic lesions in lung parenchyma. The intensity of these lesions, evaluated by the concentration of extravascular haemoglobin, was not significantly affected by pretreatment of the animals with a cyclo-oxygenase inhibitor (indomethacin), a thromboxane inhibitor (econazole) or a thromboxane antagonist (L-655,240). However, the antagonists of platelet activating factor (PAF), WEB-2086 and BN-52021, and the lipoxygenase inhibitors, nor-dihydroguaiaretic acid and L-663,536, all significantly inhibited the haemorrhagic lesions. A peptide leukotriene antagonist (L-660,711) had no effect. Furthermore, the PAF antagonists inhibited the levels of LTB4, but not of PGE2 and thromboxane, released into the bronchoalveolar space 1 h after induction of the reaction. These results suggest that the haemorrhagic lesions in this model of immune-complex alveolitis are mediated by PAF and leukotrienes, possibly LTB4.

Topics: Alveolitis, Extrinsic Allergic; Animals; Azepines; Bronchoalveolar Lavage Fluid; Dinoprostone; Diterpenes; Econazole; Ginkgolides; Hemoglobins; Hemorrhage; Indomethacin; Lactones; Leukotriene B4; Leukotrienes; Lipoxygenase Inhibitors; Male; Platelet Activating Factor; Propionates; Quinolines; Rats; Rats, Inbred Strains; Thromboxanes; Triazoles

An investigation was performed to determine whether symptom free patients with previously diagnosed extrinsic allergic alveolitis had signs of inflammation in the lung. Pulmonary clearance of inhaled technetium-99m labelled diethylene triamine penta-acetic acid (DTPA) was measured in seven patients with a history of extrinsic allergic alveolitis but with no symptoms at the time of the study and in 12 control subjects. Monoexponential clearance curves were obtained in all 12 control subjects. In contrast, lung clearance was abnormal in five of the seven patients: biexponential clearance curves were noted in four and an abnormally rapid monoexponential curve in one. Bronchoalveolar lavage was performed in all patients. Fluid from the second and third aliquots showed increased concentrations of albumin and urea in fluids from the patients, suggesting increased plasma leakage through the alveolocapillary membranes. More eosinophils and more eosinophil cationic protein were also found in the lavage fluid from the patients. The trend towards increased numbers of eosinophils in patients with abnormal lung clearance of DTPA suggests that this may be due to a continuing inflammatory reaction. Lung inflammation was also suggested by the fact that less leukotriene B4 was secreted by cultured alveolar macrophages obtained from patients than by control macrophages. It is concluded that symptom free patients with previous extrinsic allergic alveolitis have continuing alveolar disease as shown by lung clearance and lavage findings.

Topics: Adult; Albumins; Alveolitis, Extrinsic Allergic; Bronchoalveolar Lavage Fluid; Eosinophils; Humans; Leukotriene B4; Macrophages; Male; Middle Aged; Organotechnetium Compounds; Pentetic Acid; Pulmonary Alveoli; Respiratory Function Tests; Technetium Tc 99m Pentetate; Time Factors; Urea

Hypersensitivity pneumonitis (HP) is believed to be induced by immunological mechanisms, the details of which remain to be clarified. While a role for cellular immunity is accepted in the pathogenesis of HP, several clinical observations also suggest a role for immune-complex-mediated lung injury. We have previously demonstrated the presence of chemotactic factors for polymorphonuclear cells (PMNs) in bronchoalveolar lavage (BAL) fluids of acutely ill patients with the summer type of HP found in Japan. The present study correlated chemotactic factors for PMNs with the level of C5a des Arg in BAL fluids obtained from patients with summer type HP. Furthermore, this study demonstrated that PMNs were increased in BAL fluids obtained after 2 days of avoidance of exposure to the presumptive causative agent. The percentage of PMNs in the BAL increased in proportion to the activity of the chemotactic factors. Finally, leukotriene B4 was not detected in concentrated BAL or supernatant fluids of cultured macrophages. These results suggest that complement activation in the respiratory tract may occur as the early event in the pathogenesis of HP.

Topics: Alveolitis, Extrinsic Allergic; Bronchoalveolar Lavage Fluid; Chemotactic Factors; Complement Activation; Complement C3; Complement C3a; Complement C5; Complement C5a, des-Arginine; Complement System Proteins; Humans; Interleukin-8; Leukotriene B4; Neutrophils; Proteins