Differentiation and Function of Monocytes and Macrophages

居民MΦS自然栖息在腹腔液中自由漂浮。为了解决这个问题， 液体中货物吞噬效率低下，腹膜MΦS产生因子V提高其局部 在诱导炎症时，促进间质凝块的形成。血栓依次出现 将MΦS和微生物一起带出液体相，进入三维环境。这种凝血 反应通过诱导M-Φ黏附到间皮膜来共同解释 经典的“MΦ消失反应”。腹膜的多药耐药也可能需要 炎症体激活，然后可能导致细胞死亡，占较长时间 MΦ失踪的证据。事实上，当刺激MDR的刺激是强劲的时，因子V+驻留 MΦS消失了几个星期，很可能会留下腹膜腔易受影响的未来 传染性和非传染性威胁持续时间较长。我们将研究两者之间可能存在的联系 死亡和凝血，并使用谱系追踪模型来确定居民MΦS如何重新繁殖。 此外，我们还将探讨腹膜腔易患上 多药耐药后M-Φ长期丢失期间的免疫学挑战。很长一段时间 在强劲的多药耐药后MΦ丢失的可能性可能会使体腔容易受到感染。它还可能 促进其他与免疫力改变相关的疾病的进展，如癌症。在……里面 特别是，卵巢癌与腹膜腔有关，在那里它经常转移和 扩展。人类卵巢癌被认为是最具促凝性的肿瘤之一。如果是人类 存在与因子V+MΦS类似的细胞，我们在这里将对其进行研究，这种细胞可能限制肿瘤 临床上的扩张，如在小鼠身上观察到的。总体而言，我们将测试因子V+ 常驻的腹膜巨噬细胞保护腹膜免受微生物的侵袭，但也 抗卵巢肿瘤和这些巨噬细胞的促凝血活性，如果与MDR有关 通过微生物或炎症触发，可能会建立一种对肿瘤易感性增强的状态 由于失去了生长抑制肿瘤的MΦS。 相关性(请参阅说明)： 严重的临床情况可出现在腹膜腔内，从开始和进展到 败血症到癌症。这些不同的情况依赖于腹膜中的功能免疫隔间。 但是，为了更好地防治这一空间的疾病，仍有许多问题有待界定。这 其应用主要集中在常驻腹膜巨噬细胞介导的宿主防御上。

Resident MΦs naturally reside freely floating in peritoneal fluid. To counteract the problem that phagocytosis of cargo is inefficient in fluid, peritoneal MΦs produce Factor V to raise its local levels and facilitate formation of interstitial clots upon induction of inflammation. The clots in turn bring MΦs and microbes out of the fluid phase and into a 3-D environment together. This clotting reaction operates with induced MΦ adhesion onto mesothelial membranes to collectively account for the classical "MΦ disappearance reaction" (MDR). MDR in the peritoneum may also require inflammasome activation, which may then lead to cell death that accounts for an extended period of MΦ disappearance. Indeed, when the stimulus inciting the MDR is robust, Factor V+ resident MΦs disappear for several weeks, likely leaving the peritoneal cavity susceptible to future infectious and noninfectious threats for rather long durations. We will study possible links between death and coagulation and use lineage tracing models to determine how resident MΦs repopulate. Furthermore, we will investigate the idea that the peritoneal cavity is left susceptible to immunological challenges during the long duration of MΦ loss following MDR. A prolonged period of MΦ loss following a robust MDR may leave the body cavity vulnerable to infection. It may also promote progression of other diseases associated with altered immunity, like cancers. In particular, ovarian cancer is associated with the peritoneal cavity, where it often metastasizes and expands. Human ovarian cancers are considered one of the most procoagulant tumors. If human counterparts to the Factor V+ MΦs exist, which we will study herein, such cells might limit tumor expansion clinically, as observed in mice. Overall, we will test the hypothesis that Factor V+ resident peritoneal macrophages protect the peritoneal cavity from microbial pathogens but also against ovarian tumors and that the procoagulant activity of these macrophages, if linked to MDR by a microbial or inflammatory trigger, may set up a state of enhanced susceptibility to tumor growth due to loss of tumor-restricting MΦs. RELEVANCE (See instructions): Serious clinical conditions can arise in the peritoneal cavity, ranging from the initiation and progression of sepsis to cancer. These diverse conditions rely on a functional immune compartment in the peritoneal space, but there is much that remains to be defined to better combat diseases in this space. This application focuses on host defense mediated by resident peritoneal macrophages.