Sulphidopeptide leukotrienes in asthma.
Bronchial asthma is characterized by airways inflammation and airways hyperresponsiveness. It is unlikely that the pathophysiology of asthma and bronchial hyperresponsiveness can be explained on the basis of a single cell or a single class of mediators. Nevertheless, the possibility that leukotrienes may contribute to the pathogenesis of the inflammatory, vasoactive ans spasmogenic components of bronchial asthma is suggested by the properties of these lipid mediators, the preferential capacity of inflammatory cells to generate leukotrienes and the presence of leukotrienes in the airways of asthmatic subjects. The sulphidopeptide leukotrienes are potent bronchoconstrictor agonists when inhaled. The airways of asthmatic subjects are hyperresponsive to leukotrienes as to other bronchoconstrictor agonists. Nevertheless, the airways responsiveness of asthmatic subjects to these agonists demonstrate several unusual properties. While the airways of asthmatic subjects are relatively less responsive to LTC4 and LTD4, compared to agents such as histamine or methacholine, they demonstrate a marked and selective hyperresponsiveness to LTE4, suggesting a possibly unique role for this mediator in the pathogenesis of airways hyperresponsiveness. In addition an increased sensitivity of the airways to LTE4 may contribute to the mechanism of aspirin-induced asthma. The capacity of the sulphidopeptide leukotrienes to increase the airways responsiveness of normal subjects to methacholine and of asthmatic subjects to histamine is further evidence for a role for these substances in the pathogenesis of bronchial asthma.
Lee
T H
TH
Department of Allergy and Allied Respiratory Disorders, Guy's Hospital, London, UK.
O'Hickey
S P
SP
Jacques
C
C
Hawksworth
R J
RJ
Arm
J P
JP
Christie
P
P
Spur
B W
BW
Crea
A E
AE
D000818:Animals; D001241:Aspirin / Q000009:adverse effects; D001249:Asthma / Q000139:chemically induced / Q000378:metabolism*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016084:Bronchoconstriction / Q000187:drug effects; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D017999:Leukotriene E4; D016210:Methacholine Chloride / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D013189:SRS-A / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D014132:Trachea / Q000187:drug effects
D013189:SRS-A; D016210:Methacholine Chloride; D017999:Leukotriene E4; D006632:Histamine; D001241:Aspirin