|Budget Amount *help
¥3,400,000 (Direct Cost : ¥3,400,000)
Fiscal Year 1998 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1997 : ¥2,300,000 (Direct Cost : ¥2,300,000)
In iniflammatory sites, GM-CSF is mainly produced by macrophages and activated T cells. The inflammatory site is surrounded by macrophages and T cells, which are called satelite cells. Bactericidal ability of neutrophils is augmented and the cellular survival is prolonged by the treatment of GM-CSF.In contrast, G-CSF has a weaker effect, G-CSF is mainly produced by epithelium or fibroblast in stromal cells. The lower concentrations of GM-CSF enhance neutrophil chemotaxis, meanwhile the higher concentrations of GM-CSF induce the tight regulation of integrin adhesiveness and the specific localization of activated neutrophils to inflammatory sites. From these findings, GM-CSF is supposed to play as a pro-inflammatory cytokine in several diseases as ARDS and bronchial asthma.
The unnecessary prolongation of neutrophil and augmentation of bactericidal ability may produce toxic substances. The regulation of granulocyte life and function has been proposed as a key mechanism for the inhibition
of inflammatory disease and tissue damage. In bronchial asthma, cytokines as GM-CSF and IL-5 are upregulated and have been proposed to cause granulocyte infilitration in the airway. We examined the abilities of theophylline, a brochodilator, to counteract the prolongation of human granulocyte survival caused by GM-CSF and IL-5. Theophylline's effect to accelerate granulocyte apoptosis is an important immunomodulatory action in the control of bronchial asthma. In addition, we examined neutrophil apoptosis in individuals with Down syndrome (DS). Granulocyte survival is shortened in DS individuals, accerelated apoptosis of granulocytes may be a factor to prevent chronic airway inflammation and bronchial asthma in DS.The superoxide dismutase gene resides on chromosome 21, SOD may be a key enzyme in the mechanism to induce cellular apoptosis.
Behcet disease is a chronic condition in which the functions of neutrophils are characteristically increased. We examined the effect of pentoxifylline (a membrane fluidizer) in controlling Behcet disease, and further studies have been done between children's cases.
3) 気管支喘息薬であるテオフィリンが,好中球の寿命を短縮しこの作用がBcl蛋白に作用しGM-CSFやIL-5に拮抗し抗炎症作用を有するが,(J Clin Invest)この作用がアデノシンA2アンタゴニストとしての作用であることを証明した(未発表)。
4) 細胞内情報伝達を一部遮断する薬剤が,好中球機能亢進がその病因と考えられるベーチェット病に有効であること(Ann Intern Med)を報告し,小児の症例での有効性を検討した(J Pediatr).
5) 顆粒球寿命は組織障害に関係することが示唆され,ダウン症候群での顆粒球寿命の短縮と喘息罹患率の低下の関連性が判明した(Am J Med Genet)。 Less