Kazunori Yamashita1, Takeshi Nabe1, Hisao Tomioka2
and Shigekatsu Kohno1,*
1Department of Pharmacology, Kyoto Pharmaceutical University,
5 Nakauchi, Misasagi, Yamashina, Kyoto 607 - 8414, Japan
2Department of Internal Medicine, Sakura Hospital, Toho University,
564 - 1 Aza-Miyashita, Shimoshizu, Sakura, Chiba 285 - 0841, Japan
* To whom correspondence should be addressed.
Abstract: The contributions of histamine, cysteinyl leukotrienes
(CysLTs) and thromboxane A2
(TXA2) to the asthmatic responses and the magnitudes of blood
and lung eosinophilia at acute and chronic stages of our asthmatic model
were comparatively determined. Guinea pigs were alternately sensitized/challenged
by inhalation with ovalbumin+Al(OH)3 and ovalbumin, once every
2 weeks. Effects of mepyramine, pranlukast (a CysLT antagonist) and seratrodast
(a TXA2 antagonist) on the early (EAR) and/or the late asthmatic
response (LAR) were assessed at the second and fourth antigen challenges.
The second challenge caused EAR but not LAR. Although the EAR was decreased
at the fourth challenge, a substantial LAR was seen. Both mepyramine and
seratrodast inhibited the EAR at the second challenge by approximately 50%.
However, at the fourth challenge, these drugs did not inhibit the EAR. The
LAR at the fourth challenge was attenuated by pranlukast and seratrodast
by 45% and 40%, respectively. Both the blood and lung eosinophilia were
modestly and markedly induced 5 h after the second and fourth challenges,
respectively. These results strongly suggest that repetition of antigen
challenge induces quantitative alterations of chemical mediators participating
in the asthmatic responses and a change of the body state under which eosinophils
exhibit enhanced migratory activities.
Keywords: Cysteinyl leukotriene, Eosinophil, Experimental asthma,
Histamine, Thromboxane A2