High Heme and Low Heme Oxygenase-1 Are Associated with Mast Cell Activation/Degranulation in HIV-Induced Chronic Widespread Pain.
High Heme and Low Heme Oxygenase-1 Are Associated with Mast Cell Activation/Degranulation in HIV-Induced Chronic Widespread Pain.
复制标题
DOI：
10.3390/antiox12061213
复制
发表时间：
2023-06-03
期刊：
影响因子：
7
通讯作者：
Aggarwal, Saurabh
中科院分区：
文献类型：
--
作者：
Chatterjee, Tanima;Arora, Itika;Underwood, Lilly;Gryshyna, Anastasiia;Lewis, Terry L.;Masjoan Juncos, Juan Xavier;Goodin, Burel R.;Heath, Sonya;Aggarwal, Saurabh
绝大多数艾滋病毒感染者 (PWH) 一生都会经历慢性广泛性疼痛 (CWP)。之前，我们证明 PWH 联合 CWP 会增加溶血并减弱血红素加氧酶 1 (HO-1) 水平。 HO-1 将反应性无细胞血红素降解为胆绿素和一氧化碳 (CO) 等抗氧化剂。我们发现高血红素或低 HO-1 可能通过多种机制引起动物痛觉过敏。在这项研究中，我们假设高血红素或低 HO-1 导致肥大细胞活化/脱粒，导致组胺和缓激肽等疼痛介质的释放。自我报告 CWP 的 PWH 是从阿拉巴马大学伯明翰 HIV 诊所招募的。动物模型包括HO-1−/−小鼠和溶血小鼠，其中C57BL/6小鼠腹腔注射盐酸苯肼(PHZ)。结果表明，接受 CWP 治疗的 PWH 中血浆组胺和缓激肽升高。这些疼痛介质在 HO-1−/− 小鼠和溶血小鼠中也很高。在体内和体外（RBL-2H3 肥大细胞）中，血红素诱导的肥大细胞脱粒均通过 CO 供体 CORM-A1 的处理而受到抑制。 CORM-A1 还可以减轻溶血小鼠的机械性和热（冷）异常性疼痛。总之，数据表明，在细胞和动物中观察到的继发于高血红素或低 HO-1 的肥大细胞活化与 CWP 的 PWH 中血红素、组胺和缓激肽血浆水平升高相关。
An overwhelming number of people with HIV (PWH) experience chronic widespread pain (CWP) throughout their lifetimes. Previously, we demonstrated that PWH with CWP have increased hemolysis and attenuated heme oxygenase 1 (HO-1) levels. HO-1 degrades reactive, cell-free heme into antioxidants like biliverdin and carbon monoxide (CO). We found that high heme or low HO-1 caused hyperalgesia in animals, likely through multiple mechanisms. In this study, we hypothesized that high heme or low HO-1 caused mast cell activation/degranulation, resulting in the release of pain mediators like histamine and bradykinin. PWH who self-report CWP were recruited from the University of Alabama at Birmingham HIV clinic. Animal models included HO-1−/− mice and hemolytic mice, where C57BL/6 mice were injected intraperitoneally with phenylhydrazine hydrochloride (PHZ). Results demonstrated that plasma histamine and bradykinin were elevated in PWH with CWP. These pain mediators were also high in HO-1−/− mice and in hemolytic mice. Both in vivo and in vitro (RBL-2H3 mast cells), heme-induced mast cell degranulation was inhibited by treatment with CORM-A1, a CO donor. CORM-A1 also attenuated mechanical and thermal (cold) allodynia in hemolytic mice. Together, the data suggest that mast cell activation secondary to high heme or low HO-1 seen in cells and animals correlates with elevated plasma levels of heme, histamine, and bradykinin in PWH with CWP.
登录
查看更多内容
影响因子：
64.8
作者：
GORDON, JR;GALLI, SJ
通讯作者：
GALLI, SJ
影响因子：
11.4
作者：
Aggarwal, Saurabh;DeBerry, Jennifer J.;Matalon, Sadis
通讯作者：
Matalon, Sadis
影响因子：
8.7
作者：
Gupta K;Harvima IT
通讯作者：
Harvima IT
DOI：
10.1016/0141-5425(91)90110-s
发表时间：
1991-07-01
期刊：
JOURNAL OF BIOMEDICAL ENGINEERING
影响因子：
--
作者：
GASSER, B;RUSSENBERGER, ME;PERREN, SM
通讯作者：
PERREN, SM
影响因子：
3.7
作者：
Adach W;Olas B
通讯作者：
Olas B