Browsing by Subject "macrophages"

Sort by: Order: Results:

Now showing items 1-12 of 12
  • Wisgrill, Lukas; Fyhrquist, Nanna; Ndika, Joseph; Paalanen, Laura; Berger, Angelika; Laatikainen, Tiina; Karisola, Piia; Haahtela, Tari; Alenius, Harri (2022)
    Background In allergic patients, clinical symptoms caused by pollen remind of symptoms triggered by viral respiratory infections, which are also the main cause of asthmatic exacerbations. In patients sensitized to birch pollen, Bet v 1 is the major symptom-causing allergen. Immune mechanisms driving Bet v 1-related responses of human blood cells have not been fully characterized. Objective To characterize the immune response to Bet v 1 in peripheral blood in patients allergic to birch pollen. Methods The peripheral blood mononuclear cells of birch-allergic (n = 24) and non-allergic (n = 47) adolescents were stimulated ex-vivo followed by transcriptomic profiling. Systems-biology approaches were employed to decipher disease-relevant gene networks and deconvolution of associated cell populations. Results Solely in birch-allergic patients, co-expression analysis revealed activation of networks of innate immunity and antiviral signalling as the immediate response to Bet v 1 stimulation. Toll-like receptors and signal transducer transcription were the main drivers of gene expression patterns. Macrophages and dendritic cells were the main cell subsets responding to Bet v 1. Conclusions and clinical relevance In birch-pollen-allergic patients, the activated innate immune networks seem to be, in part, the same as those activated during viral infections. This tendency of the immune system to read pollens as viruses may provide new insight to allergy prevention and treatment.
  • Fontana, Flavia; Albertini, Silvia; Correia, Alexandra; Kemell, Marianna Leena; Lindgren, Rici; Mäkilä, Ermei; Salonen, Jarno; Hirvonen, Jouni Tapio; Ferrari, Franca; Almeida Santos, Helder (2018)
    Biohybrid nanosystems are at the center of personalized medicine, affording prolonged circulation time and targeting to the disease site, and serving as antigenic sources of vaccines. The optimization and functionality parameters of these nanosystems vary depending on the properties of the core particles. In this work, the effects of the core particles’ surface charge and hydrophobicity are evaluated on the nanosystem coating with vesicles derived from plasma membrane. The measured parameters are the dimensions, surface charge, shape, and stability of the biohybrid nanosystems, both in buffer and in biologically relevant media (plasma and simulated synovial fluid). Moreover, the cytocompatibility properties of the developed nanosystems are evaluated in different cell lines mimicking the target cell populations and other districts of the body involved in the distribution and elimination of the nanoparticles. Finally, the immunological profile of the particles is investigated, highlighting the absence of immune activation promoted by the nanoplatforms.
  • Oroojalian, Fatemeh; Beygi, Mohammad; Baradaran, Behzad; Mokhtarzadeh, Ahad; Shahbazi, Mohammad-Ali (2021)
    Nanotechnology has provided great opportunities for managing neoplastic conditions at various levels, from preventive and diagnostic to therapeutic fields. However, when it comes to clinical application, nanoparticles (NPs) have some limitations in terms of biological stability, poor targeting, and rapid clearance from the body. Therefore, biomimetic approaches, utilizing immune cell membranes, are proposed to solve these issues. For example, macrophage or neutrophil cell membrane coated NPs are developed with the ability to interact with tumor tissue to suppress cancer progression and metastasis. The functionality of these particles largely depends on the surface proteins of the immune cells and their preserved function during membrane extraction and coating process on the NPs. Proteins on the outer surface of immune cells can render a wide range of activities to the NPs, including prolonged blood circulation, remarkable competency in recognizing antigens for enhanced targeting, better cellular interactions, gradual drug release, and reduced toxicity in vivo. In this review, nano-based systems coated with immune cells-derived membranous layers, their detailed production process, and the applicability of these biomimetic systems in cancer treatment are discussed. In addition, future perspectives and challenges for their clinical translation are also presented.
  • Salmiheimo, Aino N. E.; Mustonen, Harri K.; Vainionpaa, Sanna A. A.; Shen, Zhanlong; Kemppainen, Esko A. J.; Seppanen, Hanna E.; Puolakkainen, Pauli A. (2016)
    Recent studies suggest that pro-inflammatory type M1 macrophages inhibit tumor progression and that anti-inflammatory M2 macrophages enhance it. The aim of this study was to examine the interaction of type M1 and M2 macrophages with pancreatic cancer cells. We studied the migration rate of fluorescein stained pancreatic cancer cells on Matrigel cultured alone or with Granulocyte- Macrophage Colony Stimulating Factor (GM-CSF) differentiated macrophages or with Macrophage Colony Stimulating Factor (M-CSF) differentiated macrophages, skewing the phenotype towards pro- and anti-inflammatory direction, respectively. Macrophage differentiation was assessed with flow cytometry and the cytokine secretion in cell cultures with cytokine array. Both GM-CSF and M-CSF differentiated macrophages increased the migration rate of primary pancreatic adenocarcinoma cell line (MiaPaCa-2) and metastatic cell line (HPAF-II). Stimulation with IL6 or IL4+ LPS reversed the macrophages' increasing effect on the migration rate of Mi-aPaCa-2 completely and partly of HPAF-II. Co-culture with MiaPaCa-2 reduced the inflammatory cytokine secretion of GM-CSF differentiated macrophages. Co-culture of macrophages with pancreatic cancer cells seem to change the inflammatory cytokine profile of GM-CSF differentiated macrophages and this might explain why also GM-CSF differentiated macrophages promoted the invasion. Adding IL6 or IL4+ LPS to the cell culture with MiaPaCa-2 and GM-CSF or M-CSF differentiated macrophages increased the secretion of inflammatory cytokines and this could contribute to the reversion of the macrophage induced increase of cancer cell migration rate.
  • Houssari, Mahmoud; Dumesnil, Anais; Tardif, Virginie; Kivela, Riikka; Pizzinat, Nathalie; Boukhalfa, Ines; Godefroy, David; Schapman, Damien; Hemanthakumar, Karthik A.; Bizou, Mathilde; Henry, Jean-Paul; Renet, Sylvanie; Riou, Gaetan; Rondeaux, Julie; Anouar, Youssef; Adriouch, Sahil; Fraineau, Sylvain; Alitalo, Kari; Richard, Vincent; Mulder, Paul; Brakenhielm, Ebba (2020)
    Objective: Lymphatics play an essential pathophysiological role in promoting fluid and immune cell tissue clearance. Conversely, immune cells may influence lymphatic function and remodeling. Recently, cardiac lymphangiogenesis has been proposed as a therapeutic target to prevent heart failure after myocardial infarction (MI). We investigated the effects of gene therapy to modulate cardiac lymphangiogenesis post-MI in rodents. Second, we determined the impact of cardiac-infiltrating T cells on lymphatic remodeling in the heart. Approach and Results: Comparing adenoviral versus adeno-associated viral gene delivery in mice, we found that only sustained VEGF (vascular endothelial growth factor)-C(C156S)therapy, achieved by adeno-associated viral vectors, increased cardiac lymphangiogenesis, and led to reduced cardiac inflammation and dysfunction by 3 weeks post-MI. Conversely, inhibition of VEGF-C/-D signaling, through adeno-associated viral delivery of soluble VEGFR3 (vascular endothelial growth factor receptor 3), limited infarct lymphangiogenesis. Unexpectedly, this treatment improved cardiac function post-MI in both mice and rats, linked to reduced infarct thinning due to acute suppression of T-cell infiltration. Finally, using pharmacological, genetic, and antibody-mediated prevention of cardiac T-cell recruitment in mice, we discovered that both CD4(+)and CD8(+)T cells potently suppress, in part through interferon-gamma, cardiac lymphangiogenesis post-MI. Conclusions: We show that resolution of cardiac inflammation after MI may be accelerated by therapeutic lymphangiogenesis based on adeno-associated viral gene delivery of VEGF-C-C156S. Conversely, our work uncovers a major negative role of cardiac-recruited T cells on lymphatic remodeling. Our results give new insight into the interconnection between immune cells and lymphatics in orchestration of cardiac repair after injury.
  • Milenova, Ioanna; Gonzalez, Marta Lopez; Quixabeira, Dafne C. A.; Santos, Joao Manuel; Cervera-Carrascon, Victor; Dong, Wenliang; Hemminki, Akseli; van Beusechem, Victor W.; van de Ven, Rieneke; de Gruijl, Tanja D. (2021)
    Immune checkpoint inhibitors have advanced the treatment of melanoma. Nevertheless, a majority of patients are resistant, or develop resistance, to immune checkpoint blockade, which may be related to prevailing immune suppression by myeloid regulatory cells in the tumor microenvironment (TME). ORCA-010 is a novel oncolytic adenovirus that selectively replicates in, and lyses, cancer cells. We previously showed that ORCA-010 can activate melanoma-exposed conventional dendritic cells (cDCs). To study the effect of ORCA-010 on melanoma-conditioned macrophage development, we used an in vitro co-culture model of human monocytes with melanoma cell lines. We observed a selective survival and polarization of monocytes into M2-like macrophages (CD14(+)CD80(-)CD163(+)) in co-cultures with cell lines that expressed macrophage colony-stimulating factor. Oncolysis of these melanoma cell lines, effected by ORCA-010, activated the resulting macrophages and converted them to a more proinflammatory state, evidenced by higher levels of PD-L1, CD80, and CD86 and an enhanced capacity to prime allogenic T cells and induce a type-1 T cell response. To assess the effect of ORCA-010 on myeloid subset distribution and activation in vivo, ORCA-010 was intratumorally injected and tested for T cell activation and recruitment in the human adenovirus nonpermissive B16-OVA mouse melanoma model. While systemic PD-1 blockade in this model in itself did not modulate myeloid or T cell subset distribution and activation, when it was preceded by i.t. injection of ORCA-010, this induced an increased rate and activation state of CD8 alpha(+) cDC1, both in the TME and in the spleen. Observed increased rates of activated CD8(+) T cells, expressing CD69 and PD-1, were related to both increased CD8 alpha(+) cDC1 rates and M1/M2 shifts in tumor and spleen. In conclusion, the myeloid modulatory properties of ORCA-010 in melanoma, resulting in recruitment and activation of T cells, could enhance the antitumor efficacy of PD-1 blockade.
  • Hamm, Alexander; Veschini, Lorenzo; Takeda, Yukiji; Costa, Sandra; Delamarre, Estelle; Squadrito, Mario Leonardo; Henze, Anne-Theres; Wenes, Mathias; Serneels, Jens; Pucci, Ferdinando; Roncal, Carmen; Anisimov, Andrey; Alitalo, Kari; De Palma, Michele; Mazzone, Massimiliano (2013)
  • Leinonen, Jussi; Leinikka, Paivi; Tarkia, Miikka; Lampinen, Milla; Emanuelov, Avishag K.; Beeri, Ronen; Kankuri, Esko; Mervaala, Eero (2022)
    The left atrial appendage (LAA) of the adult heart has been shown to contain cardiac and myeloid progenitor cells. The resident myeloid progenitor population expresses an array of pro-regenerative paracrine factors. Cardiac constructs have been shown to inhibit deleterious remodeling of the heart using physical support. Due to these aspects, LAA holds promise as a regenerative transplant. LAAs from adult mT/mG mice were transplanted to the recipient 129X1-SvJ mice simultaneously as myocardial infarction (MI) was performed. A decellularized LAA patch was implanted in the control group. Two weeks after MI, the LAA patch had integrated to the ventricular wall, and migrated cells were seen in the MI area. The cells had two main phenotypes: small F4/80+ cells and large troponin C+ cells. After follow-up at 8 weeks, the LAA patch remained viable, and the functional status of the heart improved. Cardiac echo demonstrated that, after 6 weeks, the mice in the LAA-patch-treated group showed an increasing and statistically significant improvement in cardiac performance when compared to the MI and MI + decellularized patch controls. Physical patch-support (LAA and decellularized LAA patch) had an equal effect on the inhibition of deleterious remodeling, but only the LAA patch inhibited the hypertrophic response. Our study demonstrates that the LAA transplantation has the potential for use as a treatment for myocardial infarction. This method can putatively combine cell therapy (regenerative effect) and physical support (inhibition of deleterious remodeling).
  • Judström, Ilona (Helsingfors universitet, 2009)
    In atherosclerosis, cholesterol accumulates in cholesterol-loaded macrophages (foam cells) forming cholesterol plaques in the arterial intima. Reverse cholesterol transport (RCT) is a mechanism in which HDL and its major structural protein apolipoprotein-A-1 (apoA-1) remove cholesterol from the foam cells and take it to the liver for its final excretion from the body in the faeces. An impaired removal of cholesterol from the foam cells is a potential contributor to a reduced RCT, which is related to a higher incidence of coronary heart disease. Chymase, a neutral protease of mast cells (MCs), is widely distributed in the connective tissue of most vertebrates and able to degrade apoA-1. After the degradation, HDL-particles are unable to interact with the ABCA-1 transporter protein on the surface of macrophages, which mediates efflux of cholesterol from the macrophage foam cells to HDL particles. It has been shown that chymase derived from rat peritoneal MCs is able to degrade apoA-1 even in the presence of blood plasma which contains natural inhibitors for chymase (α-2-macroglobulin and α-1-antichymotrypsin). In the present study we wanted to find out if mouse mast cell protease 4 (mMCP-4) isolated from peritoneal mast cells is able to maintain its enzymatic activity even in the presence of mouse serum and intraperitoneal fluid. A small molecular weight compound (S-2586) was used as a substrate. In the in vitro experiments a sonicated MC preparation that contains active chymase was used and the activity of chymase was measured in the presence of varying concentrations of plasma and intraperitoneal fluid. In the in vivo experiments we evaluate whether mast cell-dependent proteolysis of HDL particles does occur, and whether such modification inhibits their efficiency in inducing cellular cholesterol efflux in vitro. We found that both serum and intraperitoneal fluid inhibited chymase activity, serum to a higher extent. Systemic activation of MCs in mast cell-competent mice, but not in mast cell-deficient mice, in vivo led to a decreased ability of plasma and intraperitoneal fluid to act as cholesterol acceptors from cultured cholesterol-loaded macrophages. Local activation of peritoneal mast cells also blocked the cholesterol efflux-inducing effect of intraperitoneally injected human apoA-1. This work was performed at the Wihuri Research Institute. Licenses for animal work were approved by the Finnish Laboratory Animal Experiment Committee (Suomen eläinkoelautakunta, ELLA). Laboratory animals (female NMRI mice) were from the Viikki Laboratory Animal Centre of the University of Helsinki and the mast cell deficient strain of mice W-sash c-kit mutant KitW-sh/W-sh were from the Jackson Laboratory (BarHarbor, Maine). The work was supervised by the director of the Research Institute Petri Kovanen MD PhD and Miriam Lee-Rueckert PhD. Laboratory assistance was perceived from the technicians of the Wihuri Research Institute.
  • Heymans, Stephane; Eriksson, Urs; Lehtonen, Jukka; Cooper, Leslie T. (2016)
    Myocarditis is a diverse group of heart-specific immune processes classified by clinical and histopathological manifestations. Up to 40% of dilated cardiomyopathy is associated with inflammation or viral infection. Recent experimental studies revealed complex regulatory roles for several microribonucleic acids and T-cell and macrophage subtypes. Although the prevalence of myocarditis remained stable between 1990 and 2013 at about 22 per 100,000 people, overall mortality from cardiomyopathy and myocarditis has decreased since 2005. The diagnostic and prognostic value of cardiac magnetic resonance has increased with new, higher-sensitivity sequences. Positron emission tomography has emerged as a useful tool for diagnosis of cardiac sarcoidosis. The sensitivity of endomyocardial biopsy may be increased, especially in suspected sarcoidosis, by the use of electrogram guidance to target regions of abnormal signal. Investigational treatments on the basis of mechanistic advances are entering clinical trials. Revised management recommendations regarding athletic participation after acute myocarditis have heightened the importance of early diagnosis. (C) 2016 by the American College of Cardiology Foundation.
  • Muhammad, Sajjad; Chaudhry, Shafqat Rasul; Dobreva, Gergana; Lawton, Michael T.; Niemelä, Mika; Hänggi, Daniel (2021)
    Aneurysmal subarachnoid hemorrhage (aSAH) is a highly fatal and morbid type of hemorrhagic strokes. Intracranial aneurysms (ICAs) rupture cause subarachnoid hemorrhage. ICAs formation, growth and rupture involves cellular and molecular inflammation. Macrophages orchestrate inflammation in the wall of ICAs. Macrophages generally polarize either into classical inflammatory (M1) or alternatively-activated anti-inflammatory (M2)-phenotype. Macrophage infiltration and polarization toward M1-phenotype increases the risk of aneurysm rupture. Strategies that deplete, inhibit infiltration, ameliorate macrophage inflammation or polarize to M2-type protect against ICAs rupture. However, clinical translational data is still lacking. This review summarizes the contribution of macrophage led inflammation in the aneurysm wall and discuss pharmacological strategies to modulate the macrophageal response during ICAs formation and rupture.
  • Yang, Kun; He, Yingxia; Park, Chae Gyu; Kang, Young Sun; Zhang, Pei; Han, Yanping; Cui, Yujun; Bulgheresi, Silvia; Anisimov, Andrey P.; Dentovskaya, Svetlana; Ying, Xiaoling; Jiang, Lingyu; Ding, Honghui; Njiri, Olivia Adhiambo; Zhang, Shusheng; Zheng, Guoxing; Xia, Lianxu; Kan, Biao; Wang, Xin; Jing, Huaiqi; Yang, Meiying; Li, Wei; Wang, Yuanzhi; Xiamu, Xiding; Chen, Gang; Ma, Ding; Bartra, Sara Schesser; Plano, Gregory; Klena, John D.; Yang, Ruifu; Skurnik, Mikael; Chen, Tie (2019)
    Yersinia pestis, a Gram-negative bacterium and the etiologic agent of plague, has evolved from Yersinia pseudotuberculosis, a cause of a mild enteric disease. However, the molecular and biological mechanisms of how Y pseudotuberculosis evolved to such a remarkably virulent pathogen, Y pestis, are not clear. The ability to initiate a rapid bacterial dissemination is a characteristic hallmark of Y pestis infection. A distinguishing characteristic between the two Yersinia species is that Y pseudotuberculosis strains possess an O-antigen of lipopolysaccharide (LPS) while Y pestis has lost the O-antigen during evolution and therefore exposes its core LPS. In this study, we showed that Y pestis utilizes its core LPS to interact with SIGNR1 (CD209b), a C-type lectin receptor on antigen presenting cells (APCs), leading to bacterial dissemination to lymph nodes, spleen and liver, and the initiation of a systemic infection. We therefore propose that the loss of O-antigen represents a critical step in the evolution of Y pseudotuberculosis into Y pestis in terms of hijacking APCs, promoting bacterial dissemination and causing the plague.