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γ干扰素、肿瘤坏死因子-α和粒细胞巨噬细胞集落刺激因子激活的人中性粒细胞对巴西副球孢子菌的杀伤作用:氧代谢产物的作用

Paracoccidioides brasiliensis killing by IFN-gamma, TNF-alpha and GM-CSF activated human neutrophils: role for oxygen metabolites.

作者信息

Rodrigues D R, Dias-Melicio L A, Calvi S A, Peraçoli M T S, Soares A M V C

机构信息

Department of Microbiology and Immunology, Biosciences Institute, UNESP, CEP, São Paulo, Brazil.

出版信息

Med Mycol. 2007 Feb;45(1):27-33. doi: 10.1080/13693780600981676.

DOI:10.1080/13693780600981676
PMID:17325941
Abstract

Paracoccidioidomycosis, a deep mycosis endemic in Latin America, is a chronic granulomatous disease caused by the fungus Paracoccidioides brasiliensis. Phagocytic cells play a critical role against the fungus and several papers show the effects of activator and suppressive cytokines on macrophage and monocyte functions. However, the studies focusing on polymorphonuclear neutrophils (PMNs) antifungal functions are scarcer. Thus, the objective of the present paper was to assess the capacity of human PMNs to kill virulent P. brasiliensis strain in vitro, before and after priming with different cytokines. Moreover, the involvement of oxygen metabolites in this activity was evaluated. Nonactivated cells failed to exhibit antifungal activity. However, when these cells were IFN-gamma, TNF-alpha or GM-CSF activated, a significative fungicidal activity was detected. This process was significantly inhibited when P. brasiliensis challenge occurred in presence of catalase (CAT - a scavenger of H2O2) and superoxide dismutase (SOD - a scavenger of superoxide anion). From these results it is concluded that cytokines activation is required for P. brasiliensis killing by human PMNs, and that H2O2 and superoxide anion participate as effectors molecules in this process.

摘要

副球孢子菌病是一种在拉丁美洲流行的深部真菌病,是由巴西副球孢子菌引起的慢性肉芽肿性疾病。吞噬细胞对该真菌起着关键作用,多篇论文展示了激活因子和抑制性细胞因子对巨噬细胞和单核细胞功能的影响。然而,关注多形核中性粒细胞(PMN)抗真菌功能的研究较少。因此,本文的目的是评估人PMN在体外经不同细胞因子启动前后杀死强毒巴西副球孢子菌菌株的能力。此外,还评估了氧代谢产物在该活性中的作用。未激活的细胞未表现出抗真菌活性。然而,当这些细胞被干扰素-γ、肿瘤坏死因子-α或粒细胞-巨噬细胞集落刺激因子激活时,检测到显著的杀真菌活性。当在过氧化氢酶(CAT - 一种过氧化氢清除剂)和超氧化物歧化酶(SOD - 一种超氧阴离子清除剂)存在的情况下对巴西副球孢子菌进行攻击时,这一过程受到显著抑制。从这些结果可以得出结论,人PMN杀死巴西副球孢子菌需要细胞因子激活,并且过氧化氢和超氧阴离子在这一过程中作为效应分子发挥作用。

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