The possible role of particular leukotrienes in the allergen-induced late-phase asthmatic reaction.
Challenge with allergen may provoke an early-phase and late-phase asthmatic reaction in allergic asthmatic individuals. Although the pathogenesis of the allergen-induced late-phase asthmatic reaction (LAR) is still poorly understood, the cell types and mediators involved in this reaction are considered to be of extreme importance for the understanding of the pathogenesis of asthma. Evidence has been provided that predominantly eosinophils penetrate into the bronchioli at the beginning of the LAR. The mobilization of those eosinophils into the lung tissue is caused by the release of chemotactic factors of protein or lipid nature, most likely platelet activating factor (PAF). How these cells are finally activated to release their mediators, when they have infiltrated into the bronchioli, remains obscure. They may, however, actively contribute to the occurrence of the LAR by the release of the strongly bronchoconstrictive compound leukotriene C4 (LTC4). Our investigations have shown that eosinophils do possess the capacity to synthesize this mediator upon in-vitro challenge with the calcium ionophore A23187, zymosan particles coated with IgG and C3b (C3bi) or PAF at relatively high concentrations. As to demonstrating the possible in-vivo formation of leukotrienes, studies have been undertaken to demonstrate the excretion of a stable metabolite of LTC4, i.e. LTE4, into human urine. In our first series of investigations normal individuals were challenged via inhalation of high amounts of LTD4. Besides a bronchoconstrictive reaction and an increase in the level of maximal airway narrowing to challenge with methacholine, significant LTE4 excretion could be demonstrated in the urine. Similar studies concerning allergen provocation in allergic asthmatic individuals are now in progress.(ABSTRACT TRUNCATED AT 250 WORDS)
Bruynzeel
P L
PL
Department of Pulmonary Disease, State University Utrecht, The Netherlands.
Verhagen
J
J
D000485:Allergens / Q000633:toxicity*; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000503:physiopathology*; D006801:Humans; D015289:Leukotrienes / Q000502:physiology*
D000485:Allergens; D015289:Leukotrienes