Theophylline attenuates the neutrophil-dependent augmentation of eosinophil trans-basement membrane migration.
BACKGROUND
Recent evidence suggests that both neutrophilic and eosinophilic inflammation persist in the airways of patients with severe asthma. Neutrophils can secrete a variety of mediators which may augment the migration of eosinophils. We have reported that activated neutrophils augment the trans-basement membrane migration (TBM) of eosinophils in vitro. Theophylline has been shown to modulate some functions of both neutrophils and eosinophils. The objective of this study was to evaluate whether theophylline modulates the neutrophil-dependent augmentation of eosinophil TBM.


METHODS
Eosinophils and neutrophils were isolated from peripheral blood collected from healthy donors and were then preincubated with either 0.1 mM theophylline or the medium control. The TBM of eosinophils in response to IL-8 was evaluated in the presence or absence of neutrophils by using the chambers with a Matrigel-coated Transwell insert. The generation of O(2)(-) was evaluated by the cytochrome c reduction assay.


RESULTS
As previously reported, IL-8-stimulated neutrophils significantly augmented the TBM of eosinophils. Theophylline significantly attenuated the neutrophil-dependent augmentation of eosinophil TBM (p < 0.001) and did not directly modify the TBM of neutrophils in response to IL-8 or LTB4. Similarly, the LTB4-induced TBM of eosinophils was not modified by theophylline. Finally, theophylline attenuated the superoxide anion generation from IL-8-stimulated neutrophils on the Matrigel-coated plates.


CONCLUSIONS
Our results show that theophylline can attenuate the neutrophil-dependent augmentation of eosinophil TBM. This effect is possibly attributable to the suppression of neutrophil activation provoked by the combination of basement membrane and IL-8.
Kikuchi
Izumi
I
Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan.
Kikuchi
Shinya
S
Kobayashi
Takehito
T
Takaku
Yotaro
Y
Hagiwara
Koichi
K
Kanazawa
Minoru
M
Nagata
Makoto
M
D000328:Adult; D001485:Basement Membrane; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D004804:Eosinophils / Q000502:physiology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D016897:Respiratory Burst / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology*
D016209:Interleukin-8; D013481:Superoxides; D007975:Leukotriene B4; D013806:Theophylline