Phagocytosis via complement or Fc-gamma receptors is compromised in monocytes from type 2 diabetes patients with chronic hyperglycemia.
Phagocytosis via complement or Fc-gamma receptors is compromised in monocytes from type 2 diabetes patients with chronic hyperglycemia.
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DOI：
10.1371/journal.pone.0092977
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Schlesinger LS
中科院分区：
文献类型：
--
作者：
Restrepo BI;Twahirwa M;Rahbar MH;Schlesinger LS
2 型糖尿病患者 (DM2) 患结核病 (TB) 的风险较高，这可能是由于其单核吞噬细胞的功能缺陷所致，因为这些细胞在遏制结核分枝杆菌中发挥着关键作用。我们之前的研究结果表明，来自 DM2 的单核细胞与血清调理结核分枝杆菌的关联性降低。为了确定这种改变是否是由于补体或 Fc-γ 受体 (FcγR) 的吞噬作用缺陷所致，在本研究中，我们评估了患有和不患有 DM2 的个体的单核细胞分别对涂有 IgG 或补体的绵羊红细胞的摄取。通过单变量和多变量分析，我们发现慢性高血糖与任一受体的吞噬作用减少显着相关。该缺陷与宿主血清调理素无关，流式细胞术数据表明这并非归因于 DM2 单核细胞上这些吞噬细胞受体表达的减少。两条途径之间的正相关性（R = 0.64；p = 0.003）表明来自慢性高血糖个体的单核细胞在这些细胞的两个主要吞噬途径中存在缺陷。鉴于吞噬作用与杀灭细菌的效应机制的激活有关，这种缺陷很可能是导致 DM2 患者对结核分枝杆菌等病原体的易感性较高的因素之一。
Type 2 diabetes patients (DM2) have a higher risk of tuberculosis (TB) that may be attributed to functional defects in their mononuclear phagocytes given the critical role of these cells in Mycobacterium tuberculosis containment. Our previous findings suggest that monocytes from DM2 have reduced association with serum-opsonized M. tuberculosis. To determine if this alteration is due to defects in phagocytosis via complement or Fc-gamma receptors (FcγRs), in this study we evaluated the uptake of sheep red blood cells coated with IgG or complement, respectively, by monocytes from individuals with and without DM2. We found that chronic hyperglycemia was significantly associated with reduced phagocytosis via either receptor by univariable and multivariable analyses. This defect was independent of host serum opsonins and flow cytometry data indicated this was not attributed to reduced expression of these phagocytic receptors on DM2 monocytes. The positive correlation between both pathways (R = 0.64; p = 0.003) indicate that monocytes from individuals with chronic hyperglycemia have a defect in the two predominant phagocytic pathways of these cells. Given that phagocytosis is linked to activation of effector mechanisms for bacterial killing, it is likely that this defect is one factor contributing to the higher susceptibility of DM2 patients to pathogens like M. tuberculosis.
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影响因子：
17.1
作者：
Fabri M;Stenger S;Shin DM;Yuk JM;Liu PT;Realegeno S;Lee HM;Krutzik SR;Schenk M;Sieling PA;Teles R;Montoya D;Iyer SS;Bruns H;Lewinsohn DM;Hollis BW;Hewison M;Adams JS;Steinmeyer A;Zügel U;Cheng G;Jo EK;Bloom BR;Modlin RL
通讯作者：
Modlin RL
影响因子：
5.1
作者：
CHANG, FY;SHAIO, MF
通讯作者：
SHAIO, MF
人类巨噬细胞甘露糖受体指导结核分枝杆菌脂肪氨基氨基甘氨酸介导的吞噬体生物发生。
DOI：
10.1084/jem.20051239
发表时间：
2005-10-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kang PB;Azad AK;Torrelles JB;Kaufman TM;Beharka A;Tibesar E;DesJardin LE;Schlesinger LS
通讯作者：
Schlesinger LS
影响因子：
6.7
作者：
Dai S;Rajaram MV;Curry HM;Leander R;Schlesinger LS
通讯作者：
Schlesinger LS
影响因子：
15.9
作者：
HORWITZ, MA;SILVERSTEIN, SC
通讯作者：
SILVERSTEIN, SC