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https://www.readbyqxmd.com/read/27914035/mobilization-of-peripheral-blood-stem-cells-and-changes-in-the-concentration-of-plasma-factors-influencing-their-movement-in-patients-with-panic-disorder
#1
Marcin Jabłoński, Jolanta Kucharska Mazur, Maciej Tarnowski, Barbara Dołęgowska, Daniel Pędziwiatr, Ewa Kubiś, Marta Budkowska, Daria Sałata, Justyna Pełka Wysiecka, Arkadiusz Kazimierczak, Artur Reginia, Mariusz Z Ratajczak, Jerzy Samochowiec
In this paper we examined whether stem cells and factors responsible for their movement may serve as new biological markers of anxiety disorders. The study was carried out on a group of 30 patients diagnosed with panic disorder (examined before and after treatment), compared to 30 healthy individuals forming the control group. We examined the number of circulating HSCs (hematopoetic stem cells) (Lin-/CD45 +/CD34 +) and HSCs (Lin-/CD45 +/AC133 +), the number of circulating VSELs (very small embryonic-like stem cells) (Lin-/CD45-/CD34 +) and VSELs (Lin-/CD45-/AC133 +), as well as the concentration of complement components: C3a, C5a and C5b-9, SDF-1 (stromal derived factor) and S1P (sphingosine-1-phosphate)...
December 2, 2016: Stem Cell Reviews
https://www.readbyqxmd.com/read/27903965/tumor-associated-mesenchymal-stem-like-cells-provide-extracellular-signaling-cue-for-invasiveness-of-glioblastoma-cells
#2
Eun-Jung Lim, Yongjoon Suh, Ki-Chun Yoo, Ji-Hyun Lee, In-Gyu Kim, Min-Jung Kim, Jong Hee Chang, Seok-Gu Kang, Su-Jae Lee
Hyaluronic acid (HA) is abundant in tumor microenvironment and closely associated with invasiveness of glioblastoma (GBM) cells. However, the cellular mechanism underlying HA-rich microenvironment in GBM remains unexplored. Here, we show that tumor-associated mesenchymal stem-like cells (tMSLCs) contribute to abundance of hyaluronic acid (HA) in tumor microenvironment through HA synthase-2 (HAS2) induction, and thereby enhances invasiveness of GBM cells. In an autocrine manner, C5a secreted by tMSLCs activated ERK MAPK for HAS2 induction in tMSLCs...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27895761/c5a-receptor-expression-is-associated-with-poor-prognosis-in-urothelial-cell-carcinoma-patients-treated-with-radical-cystectomy-or-nephroureterectomy
#3
Yoshihiro Wada, Yoshihiro Maeda, Tatsuko Kubo, Ken Kikuchi, Masatoshi Eto, Takahisa Imamura
Patients with aggressive urothelial cell carcinoma (UCC) that undergo radical cystectomy or nephroureterectomy exhibit markedly high rates of disease recurrence and mortality. To select appropriate adjuvant thxerapies in addition to radical surgery, the identification of predictive prognostic markers for UCC patients is required. The aim of the present study was to identify such markers, by evaluating the association of UCC complement component 5 (C5) fragment a (C5a)receptor (C5aR) expression, detected using immunohistochemistry, with clinicopathological parameters and survival outcomes of UCC patients...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27846429/effects-of-bothrops-atrox-venom-and-two-isolated-toxins-on-the-human-complement-system-modulation-of-pathways-and-generation-of-anaphylatoxins
#4
Danilo L Menaldo, Carolina P Bernardes, Anna L Jacob-Ferreira, Cíntia G Nogueira-Santos, Tania M Casare-Ogasawara, Luciana S Pereira-Crott, Suely V Sampaio
The complement system plays important biological roles, including the activation of inflammatory processes in response to the generation of proteolytic fragments of its components. Here we evaluated the effects of Bothrops atrox venom and two of its toxins (the P-I metalloprotease Batroxase and the acidic phospholipase A2 BatroxPLA2) on the human complement system, evaluating their effects on the classical (CP), lectin (LP) and alternative (AP) pathways, as well as on different complement components associated to the generation of anaphylatoxins...
November 12, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27825984/phosphoinositide-3-kinase-%C3%AE-ties-chemoattractant-and-adrenergic-control-of-microglial-motility
#5
Nadine Schneble, Caroline Schmidt, Reinhard Bauer, Jörg P Müller, Shamci Monajembashi, Reinhard Wetzker
Microglial motility is tightly controlled by multitude of agonistic and antagonistic factors. Chemoattractants, released after infection or damage of the brain, provoke directed migration of microglia to the pathogenic incident. In contrast, noradrenaline and other stress hormones have been shown to suppress microglial movement. Here we asked for the signaling reactions involved in the positive and negative control of microglial motility. Using pharmacological and genetic approaches we identified the lipid kinase activity of phosphoinositide 3-kinase species γ (PI3Kγ) as an essential mediator of microglial migration provoked by the complement component C5a and other chemoattractants...
November 5, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27821813/enrichment-of-c5a-c5ar-axis-predicts-poor-postoperative-prognosis-of-patients-with-clear-cell-renal-cell-carcinoma
#6
Wei Xi, Li Liu, Jiajun Wang, Yu Xia, Qi Bai, Ying Xiong, Yang Qu, Qilai Long, Jiejie Xu, Jianming Guo
Anaphylatoxin C5a and its receptor C5aR on cancer cells constitute a vital axis to cancer progression. In this study, we measured C5aR level by immunohistochemistry in the same cohort of our previous C5a research, and C5a-C5aR axis status was determined by synthesizing C5a and C5aR data. C5aR was an adverse independent prognostic factor for ccRCC patients. Kaplan-Meier analyses revealed the unique position of both C5a and C5aR high population in postoperative survival, based on which patients were then shunted into C5a-C5aR enriched and non-enriched groups...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27806664/complement-c5a-is-present-in-csf-of-human-newborns-and-is-elevated-in-association-with-preterm-birth
#7
Rozalia Pataky, A Forbes Howie, Guillermina Girardi, James P Boardman
Neuroinflammation contributes to developmental brain injury associated with preterm birth, but the mediators that drive it are incompletely understood. Previous studies have shown that complement C5a is present and injurious in the brains of fetal mice exposed to preterm labour. Here, we demonstrate that C5a is present in the cerebrospinal fluid of newborn human infants, and that levels are elevated in those born preterm. The difference is not explained by systemic infection. The role of complement activation in the neonatal brain and its role as a potential therapeutic target for preterm brain injury warrants further study...
November 2, 2016: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/27784330/c5ar-inhibition-in-the-early-inflammatory-phase-does-not-affect-bone-regeneration-in-a-model-of-uneventful-fracture-healing
#8
Christian Ehrnthaller, Markus Huber-Lang, Anna Kovtun, Anna Elise Rapp, Julia Kemmler, Florian Gebhard, Anita Ignatius
BACKGROUND: Recent studies were able to demonstrate involvement of the complement cascade in bone biology. Further studies analyzed the role of complement in traumatic injuries and demonstrated negative effects after excessive systemic activation of the inflammatory response with early abrogation of complement activation after application of a C5aR-antagonist exerting beneficial effects upon bone regeneration. In contrast, own fracture healing experiments with complement-deficient animals implied a crucial role of the complement cascade for sufficient fracture healing...
October 26, 2016: European Journal of Medical Research
https://www.readbyqxmd.com/read/27784126/monitoring-of-complement-activation-biomarkers-and-eculizumab-in-complement-mediated-renal-disorders
#9
Cyrill Wehling, Oliver Amon, Martin Bommer, Bernd Hoppe, Karim Kentouche, Gesa Schalk, Rolf Weimer, Michael Wiesener, Bernd Hohenstein, Burkhard Tönshoff, Rainer Büscher, Henry Fehrenbach, Ömer-Necmi Gök, Michael Kirschfink
Various complement-mediated renal disorders are currently treated with the complement inhibitor eculizumab. By blocking the cleavage of C5 this monoclonal antibody prevents cell damage caused by complement-mediated inflammation. We included 23 patients with atypical hemolytic uremic syndrome (aHUS, n=12), C3 glomerulopathies (C3G, n=9) and acute antibody-mediated renal graft rejection (AMR, n=2), treated with eculizumab in 12 hospitals in Germany. We explored the course of complement activation biomarkers and the benefit of therapeutic drug monitoring of eculizumab...
October 26, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27782330/old-dogs-new-tricks-immunoregulatory-properties-of-c3-and-c5-cleavage-fragments
#10
REVIEW
Admar Verschoor, Christian M Karsten, Steven P Broadley, Yves Laumonnier, Jörg Köhl
The activation of the complement system by canonical and non-canonical mechanisms results in the generation of multiple C3 and C5 cleavage fragments including anaphylatoxins C3a and C5a as well as opsonizing C3b/iC3b. It is now well appreciated that anaphylatoxins not only act as pro-inflammatory mediators but as immunoregulatory molecules that control the activation status of cells and tissue at several levels. Likewise, C3b/iC3b is more than the opsonizing fragment that facilitates engulfment and destruction of targets by phagocytes...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27777575/activation-of-human-complement-system-by-dextran-coated-iron-oxide-nanoparticles-is-not-affected-by-dextran-fe-ratio-hydroxyl-modifications-and-crosslinking
#11
Guankui Wang, Fangfang Chen, Nirmal K Banda, V Michael Holers, LinPing Wu, S Moein Moghimi, Dmitri Simberg
While having tremendous potential as therapeutic and imaging tools, the clinical use of engineered nanoparticles has been associated with serious safety concerns. Activation of the complement cascade and the release of proinflammatory factors C3a and C5a may contribute to infusion-related reactions, whereas opsonization with C3 fragments promotes rapid recognition and clearance of nanomaterials by mononuclear phagocytes. We used dextran-coated superparamagnetic iron oxide nanoparticles (SPIO), which are potent activators of the complement system, to study the role of nanoparticle surface chemistry in inciting complement in human serum...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27768695/characterization-of-pharmacologic-and-pharmacokinetic-properties-of-ccx168-a-potent-and-selective-orally-administered-complement-5a-receptor-inhibitor-based-on-preclinical-evaluation-and-randomized-phase-1-clinical-study
#12
Pirow Bekker, Daniel Dairaghi, Lisa Seitz, Manmohan Leleti, Yu Wang, Linda Ertl, Trageen Baumgart, Sarah Shugarts, Lisa Lohr, Ton Dang, Shichang Miao, Yibin Zeng, Pingchen Fan, Penglie Zhang, Daniel Johnson, Jay Powers, Juan Jaen, Israel Charo, Thomas J Schall
The complement 5a receptor has been an attractive therapeutic target for many autoimmune and inflammatory disorders. However, development of a selective and potent C5aR antagonist has been challenging. Here we describe the characterization of CCX168 (avacopan), an orally administered selective and potent C5aR inhibitor. CCX168 blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils. CCX168 retains high potency when present in human blood...
2016: PloS One
https://www.readbyqxmd.com/read/27756879/c5a-receptor-cd88-promotes-motility-and-invasiveness-of-gastric-cancer-by-activating-rhoa
#13
Takayoshi Kaida, Hidetoshi Nitta, Yuki Kitano, Kensuke Yamamura, Kota Arima, Daisuke Izumi, Takaaki Higashi, Junji Kurashige, Katsunori Imai, Hiromitsu Hayashi, Masaaki Iwatsuki, Takatsugu Ishimoto, Daisuke Hashimoto, Yoichi Yamashita, Akira Chikamoto, Takahisa Imanura, Takatoshi Ishiko, Toru Beppu, Hideo Baba
PURPOSE: Anaphylatoxin C5a is a strong chemoattractant of the complement system that binds the C5a receptor (C5aR). The expression of C5aR is associated with poor prognosis in several cancers. However, the role of C5aR in gastric cancer (GC) is unknown. The aim of this study was to examine the role of C5aR on GC cell motility and invasion. EXPERIMENTAL DESIGN: The mechanism of invasion via C5aR was assessed by analyzing cytoskeletal rearrangement and RhoA activity after C5a treatment...
October 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27754115/os-23-02-the-role-of-complement-c5a-mediated-placental-dysfunction-in-the-onset-of-preeclampsia
#14
Yu Ma, Cheng-Chao Ruan, Yu Zhang, Qian Ge, Qi-Hong Wu, Ling-Ran Kong, Ping-Jin Gao
OBJECTIVE: Women with preeclampsia (PE) display excessive activation of complement system. However, little is known about the detailed cellular and molecular mechanism of complement activation in the development of PE. Here, we hypothesized that whether complement C5a contributes to the onset of PE through its effect on trophoblasts. DESIGN AND METHOD: In this study, 23 women with established PE and 32 normotensive women were recruited. At entry, peripheral and central blood pressure and pulse wave velocity (PWV) were performed...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27721145/alternative-pathway-regulation-by-factor-h-modulates-streptococcus-pneumoniae-induced-proinflammatory-cytokine-responses-by-decreasing-c5a-receptor-crosstalk
#15
Erika van der Maten, Cynthia M de Bont, Ronald de Groot, Marien I de Jonge, Jeroen D Langereis, Michiel van der Flier
Bacterial pathogens not only stimulate innate immune receptors, but also activate the complement system. Crosstalk between complement C5a receptor (C5aR) and other innate immune receptors is known to enhance the proinflammatory cytokine response. An important determinant of the magnitude of complement activation is the activity of the alternative pathway, which serves as an amplification mechanism for complement activation. Both alternative pathway activity as well as plasma levels of factor H, a key inhibitor of the alternative pathway, show large variation within the human population...
December 2016: Cytokine
https://www.readbyqxmd.com/read/27709492/c5a-c5ar-pathway-plays-a-vital-role-in-brain-inflammatory-injury-via-initiating-fgl-2-in-intracerebral-hemorrhage
#16
Bangqing Yuan, Fenlan Fu, Shaokuan Huang, Chuangan Lin, Guang Yang, Kunlong Ma, Hui Shi, Zhao Yang
Intracerebral hemorrhage (ICH) is a serious emergency with high mortality and morbidity. Up to date, a limited understanding of ICH pathogenesis is difficult to implement effective therapeutic strategy. Much evidence demonstrates that the complement cascade is activated after experimental ICH. However, the exact mechanism has not been well studied in ICH. In the current study, C57BL/6J mice were injected with autologous whole blood. C5a/C5aR levels, microglia infiltration, inflammatory cytokine, and fibrinogen-like protein 2 (Fgl-2) expression in the perihematomal region were analyzed following ICH...
October 5, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27693845/anti-inflammatory-and-anti-fibrinolytic-effects-of-thrombomodulin-alfa-through-carboxypeptidase-b2-in-the-presence-of-thrombin
#17
Shunsuke Tawara, Takumi Sakai, Osamu Matsuzaki
BACKGROUND: Thrombomodulin (TM) alfa, a recombinant human soluble TM, enhances activation of pro-carboxypeptidase B2 (pro-CPB2) by thrombin. Activated pro-CPB2 (CPB2) exerts anti-inflammatory and anti-fibrinolytic activities. Therefore, TM alfa may also have anti-inflammatory and anti-fibrinolytic effects through CPB2. However, these effects of TM alfa have not been elucidated. In the present study, we investigated the effects of TM alfa on inactivation of complement component C5a as an anti-inflammatory effect and prolongation of clot lysis time as an anti-fibrinolytic effect via CPB2 in vitro...
September 17, 2016: Thrombosis Research
https://www.readbyqxmd.com/read/27692470/complement-activation-by-cholesterol-crystals-triggers-a-subsequent-cytokine-response
#18
Nathalie Niyonzima, Bente Halvorsen, Bjørnar Sporsheim, Peter Garred, Pål Aukrust, Tom Eirik Mollnes, Terje Espevik
In the host a diverse collection of endogenous danger signals is constantly generated consisting of waste material as protein aggregates or crystalline materials that are recognized and handled by soluble pattern recognition receptors and phagocytic cells of the innate immune system. These signals may under certain circumstances drive processes leading to adverse inflammation. One example is cholesterol crystals (CC) that accumulate in the vessel wall during early phases of atherogenesis and represent an important endogenous danger signal promoting inflammation...
September 28, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27688239/expression-of-the-anaphylatoxin-c5a-receptor-in-gastric-cancer-implications-for-vascular-invasion-and-patient-outcomes
#19
Hidetoshi Nitta, Takayuki Shimose, Yasunori Emi, Takahisa Imamura, Koji Ohnishi, Tetsuya Kusumoto, Manabu Yamamoto, Kengo Fukuzawa, Ikuo Takahashi, Hidefumi Higashi, Akihito Tsuji, Yoshito Akagi, Eiji Oki, Yoshihiko Maehara, Hideo Baba
The C5a receptor (C5aR) expressed in various types of cancers is involved in C5a-induced cancer cell invasion. However, its role in gastric cancer has not yet been fully elucidated. Therefore, we studied the clinical significance of C5aR expression in gastric cancer. The association of C5aR expression in gastric cancer, determined by immunostaining using the anti-C5aR antibody, with clinicopathological parameters and outcomes was evaluated in 148 patients. Further, the association of C5aR expression in liver metastatic sites with clinicopathological parameters was investigated in a separate cohort of 58 patients who underwent hepatectomy...
November 2016: Medical Oncology
https://www.readbyqxmd.com/read/27666323/complement-component-c1q-as-potential-diagnostic-but-not-predictive-marker-of-preeclampsia
#20
Chiara Agostinis, Tamara Stampalija, Dionne Tannetta, Claudia Loganes, Liza Vecchi Brumatti, Francesco De Seta, Claudio Celeghini, Oriano Radillo, Ian Sargent, Francesco Tedesco, Roberta Bulla
PROBLEM: We have previously found that C1q is constitutively expressed by invading trophoblast and endothelial cells of decidua and contributes to vascular and tissue remodeling. Based on these findings, we sought to determine whether there were changes in the circulating level of C1q that may be used as a diagnostic and predictive marker of preeclampsia. METHOD OF STUDY: We measured the levels of C1q, C4, and complement activation products in serum or plasma of normal pregnant women and preeclamptic patients from different cohorts...
December 2016: American Journal of Reproductive Immunology: AJRI
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