Department of Molecular Medicine, University College London, WC1E 6JJ, London, UK.
Dig Dis Sci. 2011 May;56(5):1482-8. doi: 10.1007/s10620-010-1426-8. Epub 2010 Oct 9.
Neutrophils are a key part of the innate immune defence against microbes, using the respiratory burst (RB) to optimise killing and digestion. Previous studies of the neutrophil RB in Crohn's disease (CD) have yielded conflicting results.
Superoxide production in response to phorbol-myristyl acetate (PMA) was measured in neutrophils from 100 patients with CD compared to 50 healthy controls (HCs) and 50 patients with ulcerative colitis (UC). A further 22 CD and 10 HCs were studied using f-Met-Leu-Phe (fMLP), and digestion of E. coli by neutrophils was also evaluated.
The mean ± SEM PMA-stimulated RB (nmol O(2)/10(6) cells/min) was 10.86 ± 0.26 in HCs, 9.76 ± 0.23 in CD (P=0.02) and 10.04 ± 0.28 in UC (P=0.09 vs HC and 0.47 vs CD). No significant effect of age, gender or medication was observed. The RB in three patients with presumed CD was found to be in the range expected in patients with inherited neutrophil disorders. Stimulation with fMLP was calcium dependent and attenuated in patients on 5-ASA. Digestion of E. coli by neutrophils was not different in HC vs CD (21.6 vs 20.53%, P=0.60).
The significant reduction in neutrophil RB in CD does not appear to result in defective bacterial digestion and is therefore unlikely play a major role in pathogenesis. Three patients in this cohort of patients with presumed idiopathic CD were found to have a profound defect of the neutrophil RB. A high index of suspicion for such patients is prudent, as their prognosis can be improved by altering or augmenting the conventional treatment regimens employed for CD.
中性粒细胞是先天免疫防御微生物的关键部分,利用呼吸爆发(RB)来优化杀伤和消化。先前关于克罗恩病(CD)中性粒细胞 RB 的研究结果存在矛盾。
比较 100 例 CD 患者与 50 例健康对照(HC)和 50 例溃疡性结肠炎(UC)患者中性粒细胞对佛波醇肉豆蔻酸乙酯(PMA)的超氧化物产生,对另外 22 例 CD 患者和 10 例 HC 患者使用 f-Met-Leu-Phe(fMLP)进行研究,并评估中性粒细胞对大肠杆菌的消化。
PMA 刺激 RB 的平均±SEM(nmol O(2)/10(6)细胞/分钟)在 HC 中为 10.86±0.26,在 CD 中为 9.76±0.23(P=0.02),在 UC 中为 10.04±0.28(P=0.09 与 HC 相比,0.47 与 CD 相比)。未观察到年龄、性别或药物的显著影响。在三名疑似 CD 的患者中,RB 被发现处于遗传性中性粒细胞疾病患者预期范围内。fMLP 刺激是钙依赖性的,5-ASA 治疗的患者会减弱。HC 与 CD 中性粒细胞对大肠杆菌的消化无差异(21.6 与 20.53%,P=0.60)。
CD 中性粒细胞 RB 的显著减少似乎不会导致细菌消化功能缺陷,因此不太可能在发病机制中起主要作用。在本队列中,三名疑似特发性 CD 的患者被发现中性粒细胞 RB 严重缺陷。对这些患者保持高度怀疑态度是谨慎的,因为改变或增强用于 CD 的常规治疗方案可以改善他们的预后。