[Effect of montelukast on the apoptosis of lymphocytes in asthmatic rats and its molecular mechanism].
OBJECTIVE
To investigate the effect of montelukast(MK) on the apoptosis of lymphocytes and the associated molecular mechanism in asthmatic rats in vivo and in vitro.


METHODS
The asthmatic model was established by sensitizing and challenging SD rat with ovalbumin (OVA). Forty male SD rats were randomly divided into control group, asthma group, MK-treated group and Dexamethason (DXM)-treated group. T lymphocytes were labeled with CD(4)+ and CD(8)+ antibodies and then labeled with TdT-mediated dUTP nick end labeling (TUNEL) to detect apoptotic cells, and immunohistochemical staining of Fas antigen (CD95) was performed to detect Fas positive cells. The influences of MK on apoptosis and Fas antigen spontaneous expression on CD(4)+ / CD(8)+ lymphocytes in vivo and in vitro were assayed.


RESULTS
The apoptosis rates of T lymphocytes from peripheral blood and lung tissue of asthmatic rats pre-treated by MK were significantly elevated as compared with those in normal control and asthma groups. In vitro culture MK was found to induce in dose- and time-dependent manner the apoptosis of peripheral blood lymphocytes pre-treated with OVA. A synergic effect of MK and DXM was demonstrated, i.e. MK in 10(-6) mol/L concentration markedly promoted the induction of apoptosis and expression of Fas antigen by 10(-6) mol/L DXM.


CONCLUSIONS
MK could induce apoptosis of peripheral blood and lung lymphocytes (mainly CD(4)+) in asthmatic rats, which may be mediated by Fas system. The induction of apoptosis of lymphocytes by MK may contribute to anti-inflammation mechanisms. Furthermore, a synergic effect of MK and DXM on the induction of apoptosis of lymphocytes might exist.
Xian
Lewu
L
Department of Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, China.
Liang
Zong'an
Z
Liu
Chuntao
C
D000085:Acetates / Q000627:therapeutic use*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy*; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D002478:Cells, Cultured; D003521:Cyclopropanes; D008297:Male; D010047:Ovalbumin; D011804:Quinolines / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides
D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D011804:Quinolines; D013440:Sulfides; D010047:Ovalbumin; C093875:montelukast