Skin eosinophilia in patients with allergic asthma, patients with nonallergic asthma, and healthy controls. II: 20-Hydroxy-leukotriene B4 is a potent in vivo and in vitro eosinophil chemotactic factor in nonallergic asthma.
BACKGROUND
In allergic and nonallergic asthma, eosinophils play an important effector role. However, because the pathogenesis of these types of asthma seems different, the mechanisms responsible for the tissue mobilization of those cells may be different. The in vivo and in vitro migratory response of eosinophils from patients with allergic and nonallergic asthma toward 20-hydroxy-leukotriene B4 (20-OH-LTB4), which is reported here, illustrates this.


METHODS
By means of the Rebuck skin window technique the in vivo skin mobilizing capacity of intracutaneously applied buffer, LTB4, and 20-hydroxy (OH)-LTB4 was evaluated in healthy subjects (n = 6), subjects with allergic asthma (n = 14), and subjects with nonallergic asthma (n = 17). Also the in vitro chemotactic responsiveness of eosinophils from the circulation of both patient groups (both n = 8) toward buffer, LTB4, and 20-OH-LTB4 were tested by use of a microchemotaxis chamber technique.


RESULTS
Although none of the substances were capable of inducing macroscopic observable skin reactions, intracutaneously applied 20-OH-LTB4 had an almost similar capacity to mobilize eosinophils in the skin of the subjects with nonallergic asthma as allergens had in subjects with allergic asthma. In 92% of the tested subjects with nonallergic asthma significant skin eosinophilia was observed. By contrast, LTB4 did not induce significant skin eosinophilia in both patient groups compared with buffer solution. This in vivo eosinophil mobilizing capacity of 20-OH-LTB4 in subjects with nonallergic asthma was confirmed by in vitro chemotaxis studies. Dose ranges of both LTB4 and 20-OH-LTB4 proved to be potent chemoattractants for eosinophils from patients with nonallergic asthma, but not for those of healthy subjects and those with allergic asthma.


CONCLUSIONS
Our results indicate that 20-OH-LTB4 may be involved in the tissue mobilization of eosinophils in nonallergic asthma and that in vitro 20-OH-LTB4 (and LTB4) may act as potent chemotactic factors on eosinophils from those patients.
Swiss Institute of Allergy and Asthma Research, Davos.
P
P
Bruijnzeel
E
E
Storz
E
E
van der Donk
C
C
Bruijnzeel-Koomen
D000328:Adult; D001249:Asthma / Q000209:etiology / Q000473:pathology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology*; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000150:complications / Q000473:pathology*; D007975:Leukotriene B4 / Q000494:pharmacology / Q000031:analogs & derivatives; D008297:Male; D012016:Reference Values; D012867:Skin / Q000473:pathology*; D012884:Skin Window Technique
D007975:Leukotriene B4; C031571:5,12,20-trihydroxy-6,8,10,14-eicosatetraenoic acid