The Actin Cytoskeleton Responds to Inflammatory Cues and Alters Macrophage Activation.
The Actin Cytoskeleton Responds to Inflammatory Cues and Alters Macrophage Activation.
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DOI：
10.3390/cells11111806
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发表时间：
2022-05-31
期刊：
影响因子：
6
通讯作者：
Rotty, Jeremy D.
中科院分区：
文献类型：
--
作者：
Ronzier, Elsa;Laurenson, Alexander J.;Manickam, Rohini;Liu, Sophia;Saintilma, Imelda M.;Schrock, Dillon C.;Hammer, John A.;Rotty, Jeremy D.
关于一类被称为放线菌病的人类疾病的分子机制，还有很多东西有待了解。这些遗传性疾病的特征在于影响免疫细胞的肌动蛋白相关蛋白的功能丧失突变，导致人类免疫病理学。然而，关于细胞骨架失调如何促进免疫功能障碍，仍有许多有待了解。目前的研究表明，巨噬细胞肌动蛋白细胞骨架响应LPS/IFNγ刺激的双相方式，涉及细胞收缩，然后细胞扩散。通过blebbistatin抑制肌球蛋白II阻断初始收缩期并降低iNOS蛋白水平和一氧化氮分泌。相反，巨噬细胞中Arp 2/3复合物的条件性缺失减弱了扩散并增加了一氧化氮的分泌。然而，iNOS的转录并没有改变肌球蛋白II或Arp 2/3功能的损失，这表明转录后的细胞骨架调控的iNOS。与这一想法一致，蛋白酶体抑制逆转了blebbistatin的作用并挽救了iNOS蛋白水平。Arp 2/3缺陷型巨噬细胞表现出两种额外的表型：缺陷型MHCII表面定位和T细胞趋化因子CCL 22的分泌抑制。这些数据表明，肌球蛋白II和Arp 2/3之间的相互作用影响巨噬细胞的活性，并可能影响适应性先天免疫协调。破坏这种平衡可能会产生不利影响，特别是在Arp 2/3相关放线菌病的背景下。
Much remains to be learned about the molecular mechanisms underlying a class of human disorders called actinopathies. These genetic disorders are characterized by loss-of-function mutations in actin-associated proteins that affect immune cells, leading to human immunopathology. However, much remains to be learned about how cytoskeletal dysregulation promotes immunological dysfunction. The current study reveals that the macrophage actin cytoskeleton responds to LPS/IFNγ stimulation in a biphasic manner that involves cellular contraction followed by cellular spreading. Myosin II inhibition by blebbistatin blocks the initial contraction phase and lowers iNOS protein levels and nitric oxide secretion. Conversely, conditional deletion of Arp2/3 complex in macrophages attenuates spreading and increases nitric oxide secretion. However, iNOS transcription is not altered by loss of myosin II or Arp2/3 function, suggesting post-transcriptional regulation of iNOS by the cytoskeleton. Consistent with this idea, proteasome inhibition reverses the effects of blebbistatin and rescues iNOS protein levels. Arp2/3-deficient macrophages demonstrate two additional phenotypes: defective MHCII surface localization, and depressed secretion of the T cell chemokine CCL22. These data suggest that interplay between myosin II and Arp2/3 influences macrophage activity, and potentially impacts adaptive-innate immune coordination. Disrupting this balance could have detrimental impacts, particularly in the context of Arp2/3-associated actinopathies.
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影响因子：
5.8
作者：
Chauhan A;Sun Y;Sukumaran P;Quenum Zangbede FO;Jondle CN;Sharma A;Evans DL;Chauhan P;Szlabick RE;Aaland MO;Birnbaumer L;Sharma J;Singh BB;Mishra BB
通讯作者：
Mishra BB
DOI：
10.1084/jem.194.6.847
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Iellem A;Mariani M;Lang R;Recalde H;Panina-Bordignon P;Sinigaglia F;D'Ambrosio D
通讯作者：
D'Ambrosio D
影响因子：
41.2
作者：
Jain N;Vogel V
通讯作者：
Vogel V
影响因子：
4.8
作者：
Chiang, Chih-Yuan;Veckman, Ville;David, Michael
通讯作者：
David, Michael
早发作感染患者的遗传DOCK2缺乏。
DOI：
10.1056/nejmoa1413462
发表时间：
2015-06-18
期刊：
The New England journal of medicine
影响因子：
--
作者：
Dobbs K;Domínguez Conde C;Zhang SY;Parolini S;Audry M;Chou J;Haapaniemi E;Keles S;Bilic I;Okada S;Massaad MJ;Rounioja S;Alwahadneh AM;Serwas NK;Capuder K;Çiftçi E;Felgentreff K;Ohsumi TK;Pedergnana V;Boisson B;Haskoloğlu Ş;Ensari A;Schuster M;Moretta A;Itan Y;Patrizi O;Rozenberg F;Lebon P;Saarela J;Knip M;Petrovski S;Goldstein DB;Parrott RE;Savas B;Schambach A;Tabellini G;Bock C;Chatila TA;Comeau AM;Geha RS;Abel L;Buckley RH;İkincioğulları A;Al-Herz W;Helminen M;Doğu F;Casanova JL;Boztuğ K;Notarangelo LD
通讯作者：
Notarangelo LD