Involvement of inflammatory mediators in the airway responses to trimellitic anhydride in sensitized guinea-pigs.
1. We examined the effect of various pharmacological agents on the acute bronchoconstrictor response and airway microvascular leakage in a model of guinea-pig sensitization to trimellitic anhydride (TMA) a cause of low molecular weight occupational asthma in man. 2. Guinea-pigs were given intradermal injections of 0.1 ml of 0.3% TMA in corn oil; 21-28 days later, anaesthetized guinea-pigs were challenged with TMA conjugated to guinea-pig albumin by tracheal instillation. Changes in lung resistance were measured and airway microvascular leakage was quantified by measuring the extravasation of Evans blue dye into the airway tissue. 3. Sensitized guinea-pig (n = 9 in each group) were pretreated with chlorpheniramine (2.5 mg kg-1, i.v.), WEB 2086 (10 micrograms kg-1, i.v.), BW 4AC (50 mg kg-1, i.p.), nedocromil sodium (2% aerosol for 60 s) or vehicle alone. 4. Pretreatment with chlorpheniramine inhibited both the acute bronchoconstrictor response and the increase in airway microvascular leakage. WEB 2086 and nedocromil sodium partially inhibited the bronchoconstrictor response but had no significant effect on airway microvascular leakage. BW 4AC caused a non-significant reduction of the bronchoconstrictor response and airway microvascular leakage. 5. These results indicate that both the bronchoconstrictor response and the airway microvascular response in this model of sensitization is mediated to a large extent by histamine. PAF but not 5-lipoxygenase products also partially mediates the bronchoconstrictor response but not the airway microvascular leakage. Nedocromil sodium partially inhibits the bronchoconstrictor response only.
Hayes
J P
JP
Department of Thoracic Medicine, National Heart and Lung Institute, Royal Brompton National Heart & Lung Hospital, London.
Lotvall
J O
JO
Barnes
P J
PJ
Newman Taylor
A J
AJ
Chung
K F
KF
D000485:Allergens; D000818:Animals; D000906:Antibodies / Q000032:analysis; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001249:Asthma / Q000209:etiology / Q000276:immunology; D016084:Bronchoconstriction / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006168:Guinea Pigs; D006636:Histamine Release; D007114:Immunization; D007074:Immunoglobulin G / Q000032:analysis; D009784:Occupational Diseases / Q000209:etiology / Q000276:immunology; D010796:Phthalic Anhydrides / Q000009:adverse effects / Q000276:immunology*; D010972:Platelet Activating Factor / Q000502:physiology; D012137:Respiratory System / Q000187:drug effects / Q000276:immunology*; D012709:Serum Albumin / Q000276:immunology
D000485:Allergens; D000906:Antibodies; D007074:Immunoglobulin G; D010796:Phthalic Anhydrides; D010972:Platelet Activating Factor; D012709:Serum Albumin; C015559:trimellitic anhydride; D001094:Arachidonate 5-Lipoxygenase