Deletion of carboxypeptidase N delays onset of experimental cerebral malaria.
Deletion of carboxypeptidase N delays onset of experimental cerebral malaria.
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DOI：
10.1111/j.1365-3024.2012.01376.x
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发表时间：
2012-08
影响因子：
2.2
通讯作者：
Barnum SR
中科院分区：
文献类型：
--
作者：
Darley MM;Ramos TN;Wetsel RA;Barnum SR
补体在病原体感染期间促进炎症，但对其在疟疾和最严重的疾病形式--脑型疟疾中的作用知之甚少。最近的研究表明，补体过敏性毒素受体C3aR和C5aR的缺失确实改变了实验性脑疟疾(ECM)的疾病易感性。然而，这并不排除C3a和C5a介导的对ECM炎症的贡献，并增加了羧肽酶对过敏毒素活性的调节迅速超过其功能的可能性。为了解决这个问题，我们使用羧肽酶N缺陷(Cpn−/−)小鼠进行了ECM。出乎意料的是，我们发现Cpn−/−小鼠比野生型小鼠存活时间更长，但对细胞外基质完全敏感。在CPN−/−小鼠发病高峰时，CD_4~+和CD_8~+T细胞的浸润没有减少，促炎细胞因子的产生也没有相应的减少。我们的结果表明，羧肽酶参与了ECM的发病机制，研究其他羧肽酶家族和家族成员的贡献可能会更深入地了解这些酶在疟疾中所起的作用。
Complement contributes to inflammation during pathogen infections, however less is known regarding its role during malaria and, the severest form of the disease, cerebral malaria. Recent studies have shown that deletion of the complement anaphylatoxins receptors, C3aR and C5aR, does alter disease susceptibility in experimental cerebral malaria (ECM). This does not however, preclude C3a- and C5a-mediated contributions to inflammation in ECM and raises the possibility that carboxypeptidase regulation of anaphylatoxin activity rapidly over rides their functions. To address this question we performed ECM using carboxypeptidase N-deficient (CPN−/−) mice. Unexpectedly, we found that CPN−/− mice survived longer than wild type mice but were fully susceptible to ECM. CD4+ and CD8+ T cell infiltration was not reduced at the peak of disease in CPN−/− mice and there was no corresponding reduction in pro-inflammatory cytokine production. Our results indicate that carboxypeptidases contribute to the pathogenesis of ECM and that, studies examining the contribution of other carboxypeptidase families and family members may provide greater insight into the role these enzymes play in malaria.
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影响因子：
5.4
作者：
Wohler, Jillian E.;Smith, Sherry S.;Zinn, Kurt R.;Bullard, Dan C.;Barnum, Scott R.
通讯作者：
Barnum, Scott R.
DOI：
10.4049/jimmunol.0804207
发表时间：
2009-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Mueller-Ortiz SL;Wang D;Morales JE;Li L;Chang JY;Wetsel RA
通讯作者：
Wetsel RA
影响因子：
4.4
作者：
Sato, T;Miwa, T;Okada, H
通讯作者：
Okada, H
影响因子：
3.6
作者：
Matthews, KW;Mueller-Ortiz, SL;Wetsel, RA
通讯作者：
Wetsel, RA
影响因子：
2.6
作者：
Campbell, WD;Lazoura, E;Okada, H
通讯作者：
Okada, H