Neutrophils from asthmatics exhibit diminished responsiveness to 2-chloroadenosine which is reversed by theophylline. Evidence for a cyclic-AMP-independent pathway on human neutrophils.
Neutrophils from asthmatics exhibit diminished responsiveness to 2-chloroadenosine which is reversed by theophylline. Evidence for a cyclic-AMP-independent pathway on human neutrophils.
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哮喘患者的中性粒细胞对 2-氯腺苷的反应性减弱，茶碱可以逆转这一情况。
DOI：
10.1007/bf00918951
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发表时间：
1992
期刊：
影响因子：
5.1
通讯作者：
Borish,L
中科院分区：
文献类型：
--
作者：
Joseph,BZ;Sustiel,AM;Borish,L
我们之前的研究表明，哮喘患者的中性粒细胞（pmn）比正常人有更强的呼吸爆发刺激，并且暴露于2-氯腺苷（2-CADO）对其呼吸爆发的抑制明显更少。目前的研究调查了这种对2-CADO反应缺陷的基础。与对照组（1.05±0.17 nmol）相比，未服用茶碱（减去茶碱）或服用茶碱（加茶碱）的哮喘患者获得的PMNs在2×10−8M FMLP(2.08±0.36 nmol/5×105 PMNs（减去茶碱）（P<0.01）产生的超氧化物显著增加(2.16±0.44（加茶碱）（P<0.01）。在FMLP （2×10−8M）存在的情况下，与对照组相比，来自负茶碱组的PMNs具有较少的2-CADO（10−6M）介导的超氧化物生成抑制(38.3±3.8% vs. 67±3.8%;（P<0.001）。加茶碱组的抑制值与对照组相似（64.5±7.2%）。在生理浓度为2-CADO （0.1μM）时，茶碱对正常小鼠呼吸性烧伤的抑制作用显著（0、10和100μM时分别为74.1±5.9%、80.1±4.9% （P<0.02）和84.7±3.8% (P<0.02)）。未服用茶碱组PMNs抑制值分别为46.2±6%、53.8±6.6% （P=NS）和63.2±7.1% （P<0.01）。正常对照静息PMNs产生0.97±0.20 pmol cAMP/107细胞，而0.1μM 2-CADO压力下产生2.83±0.75 pmol cAMP/107细胞。2-CADO与茶碱（10-100μM）联合产生的cAMP浓度与单独使用2-CADO时无显著差异。这些发现支持在PMNs中存在一种新的camp独立腺苷受体。10−8m3h标记的2-CADO的特异性结合（以Δ cpm计）在加茶碱组、减茶碱组和对照组分别为10,358±1502（与对照组相比P < 0.001）、5468±843（与对照组相比NS）和3751±477。与未暴露PMNs（3768±656;P < 0.05）相比，暴露于10 μM茶碱30分钟的正常对照PMNs中[3H]2-CADO的特异性结合（6013±969）表明，这种特异性结合的上调可能反映了茶碱的影响。这些数据支持茶碱在哮喘治疗中的抗炎作用机制，并提示这可能通过增强抗炎介质腺苷而发生。
We have shown previously that neutrophils (PMNs) from patients with asthma have a more potent stimulated respiratory burst than normals and that their respiratory burst is significantly less suppressed with exposure to 2-chloroadenosine (2-CADO). The present studies investigated the basis of this defect in responsiveness to 2-CADO. PMNs obtained from asthmatics either not on theophylline (minus theophylline) or taking theophylline (plus theophylline) generated significantly more superoxide in response to 2×10−8M FMLP (2.08±0.36 nmol/5×105 PMNs (minus theophylline) (P<0.01 compared to controls) vs. 2.16±0.44 (plus theophylline) (P<0.01) as compared to controls (1.05±0.17 nmol). In the presence of FMLP (2×10−8M), PMNs from the minus theophylline cohort had less 2-CADO (10−6M) -mediated suppression of superoxide generation as compared to controls (38.3±3.8% vs. 67±3.8%; (P<0.001). The plus theophylline group exhibited suppression values similar to controls (64.5±7.2%). Theophylline, in the presence of a physiological concentration of 2-CADO (0.1μM) accentuated the suppression of the respiratory burnt in normals (74.1±5.9%, 80.1±4.9% (P<0.02) and 84.7±3.8% (P<0.02) at 0, 10, and 100μM, respectively). PMNs from asthmatics not taking theophylline demonstrated suppression values of 46.2±6%, 53.8±6.6% (P=NS), and 63.2±7.1% (P<0.01), respectively. Resting PMNs from normal controls generated 0.97±0.20 pmol cAMP/107cells compared to 2.83±0.75 pmol in the pressnce of 0.1μM 2-CADO. The combination of 2-CADO and theophylline (10–100μM) produced cAMP concentrations not significantly different from that observed with 2-CADO alone. These findings support the existence of a novel cAMP-independent adenosine receptor in PMNs. The specific binding of 10−8M3H-labeled 2-CADO (in Δ cpm) was 10,358 ± 1502 (P < 0.001 compared to controls), 5468 ± 843 (NS compared to controls), and 3751 ± 477 in the plus theophylline group, minus theophylline group, and controls, respectively. Such up-regulation of specific binding may represent the effects of theophylline as shown by the specific binding of [3H]2-CADO in PMNs from normal controls exposed to 10 μM theophylline for 30 min (6013 ± 969) compared to unexposed PMNs (3768 ± 656; P < 0.05). These data support an antiinflammatory mechanism of action for theophylline in the therapy of asthma and suggest that this may occur through potentiation of the antiinflammatory mediator adenosine.