M(+) group a streptococci are phagocytized and killed in whole blood by C5a-activated polymorphonuclear leukocytes.

M(+) group a streptococci are phagocytized and killed in whole blood by C5a-activated polymorphonuclear leukocytes.
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M( ) a 组链球菌在全血中被 C5a 激活的多形核白细胞吞噬并杀死。

DOI:
10.1128/iai.70.1.350-359.2002
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发表时间:
2002
影响因子:
3.1
通讯作者:
Cleary,Patrick
Cleary,Patrick
中科院分区:
医学2区
文献类型:
--
作者:
DeMaster,Eric;Schnitzler,Norbert;Cheng,Qi;Cleary,Patrick

文献摘要

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历史上,通过在人血液中孵育A组链球菌并比较孵育前后的CFU数量来确定对吞噬作用的抗性。利用流式细胞术为基础的技术,我们研究了M+ A组链球菌的吞噬作用的多形核白细胞(PMN)在肝素化的人外周全血。用无毒的荧光染料对链球菌进行细胞内标记,使我们能够在存在或不存在C5 a(一种生理上重要的中性粒细胞趋化激活剂)的情况下,对全血中中性粒细胞对M+链球菌的缔合和吞噬作用进行定量。我们发现对吞噬作用有抵抗力的A组链球菌野生型菌株(由经典的兰斯菲尔德方法测定)容易与C5 a激活的全血中性粒细胞结合。在没有调理M型特异性抗体的情况下,与PMN相关的M+链球菌被吞噬并被杀死。此外,用抗人CD 11b单克隆抗体阻断β 2整合素CD 11b/CD 18可抑制M+链球菌与C5 a激活的PMN之间的结合。这些发现建立了一个新的M+链球菌和中性粒细胞之间的关系,其中C5 a激活的中性粒细胞有能力杀死M+链球菌在全血中通过受体介导的吞噬机制。
Historically, resistance to phagocytosis has been determined by incubating group A streptococci in human blood and comparing the numbers of CFU before and after incubation. Utilizing a flow cytometry-based technique, we have investigated the phagocytosis of M+group A streptococci by polymorphonuclear leukocytes (PMNs) in heparinized human peripheral whole blood. Intracellular labeling of streptococci with a nontoxic fluorescent dye allowed us to quantify the association and phagocytosis of M+streptococci by PMNs in whole blood in the presence or absence of C5a, a physiologically important chemotactic activator of PMNs. We found that wild-type strains of group A streptococci that are resistant to phagocytosis (determined by the classical Lancefield method) readily associate with C5a-activated whole-blood PMNs. In the absence of opsonizing M-type-specific antibodies, the M+streptococci associated with PMNs are phagocytized and killed. In addition, blockade of the β2integrin, CD11b/CD18, with anti-human CD11b monoclonal antibody inhibited association between M+streptococci and C5a-activated PMNs. These findings establish a new relationship between M+streptococci and PMNs, in which C5a-activated PMNs have the capacity to kill M+streptococci in whole blood through a receptor-mediated phagocytic mechanism.