Cystic fibrosis pseudomonas opsonins. Inhibitory nature in an in vitro phagocytic assay.

Cystic fibrosis pseudomonas opsonins. Inhibitory nature in an in vitro phagocytic assay.
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囊性纤维化假单胞菌调理素。

DOI:
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发表时间:
1981
影响因子:
15.9
通讯作者:
H. Reynolds
H. Reynolds
中科院分区:
医学1区
文献类型:
--
作者:
Robert B. Fick;GARYP. Naegel;Richard A. MATrHAY;H. Reynolds

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铜绿假单胞菌感染在囊性纤维化(CF)患者的慢性呼吸道疾病中起主要致病作用。尽管有明显的体液免疫应答,反映在血清和痰中高水平的抗假单胞菌抗体,抗体不消除这种细菌。在本研究中,我们已经使用亲和层析与脂多糖取代的免疫吸附凝胶分离高滴度(平均CF = 1:256)的免疫型特异性假单胞菌IgG抗体从9 CF受试者的血清中,并评估了这些抗体的功能能力,以促进吞噬和细胞内杀伤铜绿假单胞菌在体外人肺泡巨噬细胞培养系统。吞噬和细胞内杀菌动力学揭示CF IgG抗体以抑制方式起作用。与适当的阳性对照(超免疫血清,HIS;[比率HIS = 399;摄取HIS = 29 x 10(3),P <0.005])相比,吞噬率(比率CF = 204 cpm/单位时间)和120 min时的最大绝对细菌摄取(摄取CF = 18 x 10(3)14 C cpm)均受到抑制。这种CF衍生的调理素增强巨噬细胞胞内杀菌过程的能力轻度受损(细菌存活CF = 15 × 10(3)菌落形成单位(CFU)/min,存活HIS = 9 × 10(3))。通过免疫球蛋白分子的Fab和Fc部分的功能研究评估的该缺陷的进一步表征揭示了这些特异性抗体与肺泡巨噬细胞膜Fc γ受体的附着受损。这些免疫球蛋白的理化性质的初步研究是正常的。这种抑制活性在体内的表达可促进假单胞菌定殖和随后在CF受试者的呼吸道中建立的感染。
Pseudomonas aeruginosa infection plays a primary pathogenetic role in the chronic respiratory tract disease of cystic fibrosis (CF) patients. Despite pronounced humoral immune responses, reflected by high levels of antibodies against Pseudomonas in serum and in sputum, the antibodies do not eliminate this bacterium. In the present study we have used affinity chromatography with a lipopolysaccharide substituted immunoadsorbent gel to isolate high titers (meanCF = 1:256) of immunotype specific Pseudomonas IgG antibodies from the sera of nine CF subjects, and have evaluated the functional ability of these antibodies to promote phagocytosis and intracellular killing of P. aeruginosa in an in vitro human alveolar macrophage culture system. The phagocytic and intracellular bactericidal kinetics revealed that CF IgG antibodies function in an inhibitory fashion. Both the rate of phagocytosis (rateCF = 204 cpm/unit time) and absolute bacterial uptakes maximal at 120 min (uptakeCF = 18 x 10(3) 14C cpm) were inhibited compared with appropriate positive controls (hyperimmune serum, HIS; [rateHIS = 399; uptakeHIS = 29 x 10(3), P less than 0.005]). The ability of such CF-derived opsonins to potentiate macrophage intracellular bactericidal processes was mildly impaired (bacterial survivalCF = 15 x 10(3) colony forming units (CFU)/min, survivalHIS = 9 x 10(3)). Further characterization of this defect, assessed with functional studies of the Fab and Fc portions of the immunoglobulin molecule, revealed an impairment in the attachment of these specific antibodies to the alveolar macrophage membrane Fc gamma receptors. Preliminary studies of the physical-chemical properties of these immunoglobulins were normal. The expression of this inhibitory activity in vivo may facilitate Pseudomonas colonization and the subsequent established infections in the respiratory tracts of CF subjects.
肺宿主防御。
DOI: 10.1097/00005382-199810000-00003
发表时间: 1998
期刊: Journal of thoracic imaging.
影响因子: --
作者:
Twigg3rd,HL
通讯作者: Twigg3rd,HL