[The effects of anti-inflammatory and anti-asthmatic agents on CD34+ hematopoietic cells in bone marrow of asthmatic mice].
OBJECTIVE
To observe the effects of glucocorticoids and cysteinyl leukotrienes 1 receptor antagonist on CD(34)(+) hematopoietic cells, and to study the rationality of a bone marrow-targeting anti-inflammatory strategy.


METHODS
Twenty-four BALB/c mice were sensitized and challenged by 1% ovalbumin (OVA) to establish the asthmatic model. Asthmatic mice were challenged by 1% OVA and divided into 4 groups: fed by sterile saline (group A), prednisone (group B), montelukast (group C) and prednisone plus montelukast (group D) respectively for two consecutive weeks. The mice were killed at 24 h after the last challenge, then bronchoalveolar lavage fluid (BALF), peripheral blood and bone marrow were prepared. Eosinophils in peripheral blood and BALF, nucleate cells in BALF, peripheral blood and bone marrow were counted. The percentage of CD(34)(+) cells, CD(4)(+), CD(8)(+) T lymphocyte to nucleate cells in peripheral blood and bone marrow were counted by flow cytometry. Immunocytochemistry and in situ hybridization were employed to detect the hematopoietic cells expression of CD(34)(+) and IL-5Ralpha mRNA in bone marrow (CD(34)(+) IL-5Ralpha mRNA(+) cells).


RESULTS
The number of EOS in BALF and peripheral blood and the number of CD(34)(+) cells in peripheral blood and bone marrow in group A were [(18.3 +/- 1.3) x 10(5)/L], [(2.5 +/- 0.4) x 10(8)/L], [(9.6 +/- 5.1) x 10(7)/L] and [(7.7 +/- 3.2) x 10(7)/femur] respectively, compared with the corresponding indices in group B [(4.6 +/- 1.7) x 10(5)/L, (1.5 +/- 0.3) x 10(8)/L, (3.9 +/- 2.1) x 10(7)/L, (3.3 +/- 1.8) x 10(7)/femur] and group D [(3.7 +/- 1.4) x 10(5)/L, (1.7 +/- 0.3) x 10(8)/L, (4.1 +/- 1.8) x 10(7)/L, (2.2 +/- 0.7) x 10(7)/femur]; the differences all were significant (all P < 0.01). The number of bone marrow CD(34)(+) IL-5Ralpha mRNA(+) in group B and D were (23 +/- 7)% and (21 +/- 4)%, as compared with the corresponding index in group A [(37 +/- 4)%], the differences were significant (P < 0.01); the number of eosinophils in BALF in group C was (12.2 +/- 1.1) x 10(5)/L, as compared with the corresponding index in group A [(18.3 +/- 1.3) x 10(5)/L], the difference was significant (P < 0.05).


CONCLUSIONS
Prednisone probably inhibits the proliferation, differentiation and emigration of CD(34)(+) cells in the bone marrow of asthmatic mice, and inhibits eosinophilopoiesis in bone marrow, eosinophil migration into peripheral blood and recruitment to the airways. Montelukast may suppress eosinophil infiltrating into lungs of asthmatic mice, but it does not inhibit the proliferation and emigration of CD(34)(+) cells and does not show apparent synergistic effect with prednisone.
Mao
Hui
H
Department of Respiratory Medicine, West China Hospital Sichuan University, Chengdu 610041, China.
Wang
Zeng-li
ZL
Liu
Chun-tao
CT
Yin
Kai-sheng
KS
Yu
Yun-hai
YH
Deng
Yi-ling
YL
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018952:Antigens, CD34 / Q000378:metabolism*; D001249:Asthma / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003521:Cyclopropanes; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D053666:Interleukin-5 Receptor alpha Subunit; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011241:Prednisone / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics; D013440:Sulfides
D000085:Acetates; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D018952:Antigens, CD34; D003521:Cyclopropanes; C485918:IL5RA protein, human; D053666:Interleukin-5 Receptor alpha Subunit; D011804:Quinolines; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D013440:Sulfides; C093875:montelukast; D011241:Prednisone