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The complement system at the embryo implantation site
No full textThe Complement (C) system plays an important role in the control of infectious agents and in the removal of immune complexes and apoptotic cells. Like other components of innate immunity, C is able to recognize the targets through the early components and to attack them through the biologically active products released as a result of activation.
While recognition is restricted to harmful agents, the effector phase associated with the activation products of the terminal components is not selective for foreign targets and may also attack host cells. Thus, C can be considered an effective defence system but also a potential danger that may differently affect various tissues and organs.
The protective function of the C system is particularly important during pregnancy since the implanted embryo is vulnerable to attack by pathogens that colonize the cervico-vaginal cavity. Uncontrolled complement activation is prevented in successful pregnancy by the regulatory proteins positioned on the surface of several placental cells, however, unrestricted C activation induced by antibody-dependent and independent mechanisms may overcome the neutralizing effect of the C inhibitors and results in tissue damage and poor pregnancy outcome.
C components produced at feto-maternal interface serve an important function in placental development. C1q synthesized by decidual endothelial cells and expressed on the cell surface is particularly important in this regard because it acts as a molecular bridge between endovascular trophoblast and endothelial cells. C1q is also produced by trophoblast and is used to favour trophoblast migration through the decidua. Defective expression of C1q by trophoblast is associated with impaired trophoblast invasion of decidua and may have important implications in pregnancy disorders such as preeclampsia characterized by reduced vascular remodeling.
In conclusion the C system behaves as a double-edged sword, exerting a protective function and inducing damage in pathological situations that may result in poor pregnancy outcome
Beyond the Norm: The emerging interplay of complement system and extracellular matrix in the tumor microenvironment
Full text linkGround-breaking awareness has been reached about the intricate and dynamic connection between developing tumors and the host immune system. Being a powerful arm of innate immunity and a functional bridge with adaptive immunity, the complement system (C) has also emerged as a pivotal player in the tumor microenvironment (TME). Its “double-edged sword” role in cancer can find an explanation in the controversial relationship between C capability to mediate tumor cell cytolysis or, conversely, to sustain chronic inflammation and tumor progression by enhancing cell invasion, angiogenesis, and metastasis to distant organs. However, comprehensive knowledge about the actual role of C in cancer progression is impaired by several limitations of the currently available studies. In the current review, we aim to bring a fresh eye to the controversial role of C in cancer by analyzing the interplay between C and extracellular matrix (ECM) components as potential orchestrators of the TME. The interaction of C components with specific ECM components can determine C activation or inhibition and promote specific non-canonical functions, which can, in the tumor context, favor or limit progression based on the cancer setting. An in-depth and tumor-specific characterization of TME composition in terms of C components and ECM proteins could be essential to determine their potential interactions and become a key element for improving drug development, prognosis, and therapy response prediction in solid tumors
Endothelial cells are a target of both complement and kinin system.
No full textThe endothelium is a continuous physical barrier that regulates coagulation and selective passage of soluble molecules and circulating cells through the vessel wall into the tissue. Endothelial cells may contact components of the complement, the kinin and the coagulation systems and their functional activity can be influenced by these interactions. Therefore, complement activation products can induce pro-inflammatory and pro-coagulant responses by endothelial cells. Moreover complement can regulate the release of kinins on the endothelial cell surface influencing the vascular leakage. The aim of this review is to discuss the complex interplay that can be established among the endothelium, the complement proteins or its activation products, and the kinin system
Complement activation in animal and human pregnancies as a model for immunological recognition
No full textPregnancy is a most intriguing feature of biology, not at least because of the need to regulate the maternal immune response against fetal antigens. The mammalian embryo expresses paternal antigens foreign to the mother's immune system and thus elicits an immune response that can lead to fetal rejection and bad pregnancy outcomes such as recurrent miscarriages and preeclampsia. More effective strategies to prevent these pregnancy complications should be forthcoming once the underlying pathophysiological mechanisms that are involved in fetal rejection are completely understood. Our goal in writing this review is to discuss the crucial role of the complement system as an effector mechanism in placental and fetal damage that leads to bad pregnancy outcomes. Important information about the role of excessive complement activation and bad pregnancy outcomes was obtained from animal models. That uncontrolled complement activation puts at risk the survival of the fetus was reported in mouse models of recurrent miscarriages and preeclampsia. Interestingly, several observations described in the mouse models were confirmed in humans. Increased circulating levels of complement proteins, and their activation fragments were found in patients with preeclampsia, recurrent miscarriages and intrauterine growth restriction. Studies performed in animals and humans demonstrated the deleterious effect of complement activation on pregnancy outcomes. However, we also described in this article the strategic role of complement component C1q in normal placentation. C1q deserves special consideration for its role in promoting trophoblast invasion of deciduas, a crucial step in normal placental development. In conclusion, in this review we discussed all the available results of basic and clinical studies on the role of the complement system in pregnancy to expand the understanding of the pathophysiology of pregnancy complications
Emerging Roles of the Complement System at Foeto-maternal Interface
No full textThe complement system is one of the major components of humoral innate immunity, acting as one of the first lines of defence against microbes, but new roles in inflammatory and immunological processes are emerging. The placenta undergoes
an intense process of tissue remodelling which leads to the activation of the complement (C) system resulting in the release of potentially destructive activation products that need to be neutralized. The protection of the foetus against maternal C activation products is achieved by the surface expression of regulators. The liver is the main source of the plasma C components although extra-hepatic synthesis in several tissues and organs has been documented. The data collected recently indicate that trophoblast cells are able to secrete C3 and C4 and the recognition molecule C1q, contributing to the local synthesis at the placental level. Besides trophoblast cells, decidual endothelial cells acquire the ability to synthesize and express C1q on the cell surface. All these observations support the role of C1q in the placental development and its importance in trophoblast endovascular and interstitial invasion. In conclusion it is increasingly evident that a new role of complement and in particular C1q in the processes of tissue homeostasis as well as is in inflammation and infection is now emerging
Effect of a standardized liver and spleen fraction of peptides on the differentiation of human monocyte derived macrophages.
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