• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 373
  • 118
  • 77
  • 50
  • 22
  • 6
  • 5
  • 5
  • 4
  • 2
  • 1
  • 1
  • 1
  • 1
  • 1
  • Tagged with
  • 846
  • 151
  • 123
  • 115
  • 89
  • 79
  • 68
  • 65
  • 63
  • 61
  • 55
  • 49
  • 49
  • 49
  • 48
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
41

The roles of macrophage migration inhibitory factor in human neuroblastoma development

Chan, Hiu-man, 陳曉雯 January 2006 (has links)
published_or_final_version / abstract / Surgery / Doctoral / Doctor of Philosophy
42

Regulation of hormone-sensitive lipase in mouse macrophages

Harrison, Jillian A. January 1999 (has links)
No description available.
43

The Role of Monocytes and Macrophages Pathogenesis of HIV and SIV-Associated Cardiovascular Disease

Walker, Joshua Aaron January 2016 (has links)
Thesis advisor: Welkin Johnson / HIV associated cardiovascular disease is likely due to multiple factors ranging from accelerated aging, the direct effects of HIV proteins, and increased inflammation and immune activation. Monocytes/macrophages play roles in the development and progression of HIV and cardiovascular disease. Increased monocyte/macrophage inflammation and immune activation associated with HIV infection likely contributes to the increased risk of cardiovascular disease development associated with HIV infection. To further understand the role of monocytes/macrophages in the development of HIV-associated cardiovascular disease we: 1) assessed monocyte activation longitudinally to determine if they correlate with and can be predictive of cardiac fibrosis and inflammation; 2) we examined cardiac tissues from the SIV-infected CD8+ T-lymphocyte depleted animals to determine the effects of monocyte/macrophage inflammation on cardiac fibrosis; 3) in parallel we examined cardiovascular tissues from HIV+ individuals on durable cART to determine if aortic and cardiac inflammation persists with infection and if soluble factors (sCD163) correlated with intima-media thickness and fibrosis; 4) we next examined the effects of blocking leukocytes trafficking to the heart on SIV-associated cardiac inflammation and fibrosis; 5) and finally we examined if targeting monocyte/macrophage activation (as opposed to traffic) directly using MGBG decreases SIV-associated cardiovascular pathology, inflammation and fibrosis. We found that early increased monocyte activation was predictive of animals that developed cardiac fibrosis and SIV encephalitis (SIVE). Animals with both cardiac fibrosis and SIVE had increased macrophage inflammation in the heart, suggesting that there is a link between cardiac and CNS inflammation seen with HIV infection (Chapter 2). We found in a SIV-infected CD8+ T-lymphocyte depletion model of rapid AIDS increased prevalence of cardiac disease compared to nondepleted animals, and increased cardiac inflammation that correlated with cardiac fibrosis. Monocyte/macrophage traffic to the heart occurred later with SIV infection, possibly with the development of AIDS (Chapter 3). In post-mortem human tissues studies we found that inflammation in aorta and heart correlated with increased soluble CD163, and correlated with aortic intima-media thickness and cardiac fibrosis with HIV infection (Chapter 4). Blocking leukocyte traffic to the heart using an anti-α4 antibody decreased macrophage inflammation in the heart that correlated with decreased cardiac fibrosis (Chapter 5). Using MGBG, a polyamine biosynthesis inhibitor that directly targets monocyte/macrophage activation, we found decreased inflammation in the carotid artery and heart correlated with decreased carotid artery intima-media thickness and cardiac fibrosis (Chapter 6). Overall these studies provide evidence for ongoing monocyte/macrophage cardiovascular inflammation with HIV and SIV infection. Macrophage inflammation correlates with markers of cardiovascular disease (fibrosis and intima-media thickness, cardiomyocyte damage). Directly targeting monocyte/macrophage traffic (anti-α4 antibody) and activation (MGBG) decreased cardiovascular pathology, inflammation, fibrosis, and intima-media thickness. Taken together, the data in this thesis indicate that targeting monocytes/macrophages in conjunction with combination anti-retroviral therapy could alleviate cardiovascular disease in HIV-infected individuals. / Thesis (PhD) — Boston College, 2016. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.
44

The role of mammalian target of rapamycin (mTOR) in macrophage polarization

Byles, Vanessa A. January 2013 (has links)
Macrophages are key orchestrators of the innate immune response with a dynamic role in the promotion and resolution of inflammation. Macrophage polarization to a pro-inflammatory or anti-inflammatory phenotype must be tightly controlled to maintain appropriate responses to stimuli as well as to maintain tissue homeostasis. The nutrient and energy sensor Mammalian Target of Rapamycin (mTOR) integrates upstream signals from the PI3K/Akt pathway to orchestrate cellular protein, lipid, and glucose metabolism. This key metabolic pathway has been implicated in T-helper cell skewing and in the innate immune regulation. The mechanisms of innate immune regulation by mTOR are currently unclear as most studies use pharmacological inhibitors with potential off target effects. In this study, we use a novel model of TSC1 deficiency in myeloid lineage cells to elucidate a role for mTOR in macrophage polarization. We show, for the first time, that Tsc1-deficiency and constitutive mTORC1 activity in macrophages leads to a marked defect in M2 polarization when stimulated with the Th2 cytokine IL-4. Tsc1-deficient macrophages display attenuated Akt signaling in response to IL-4 consistent with negative feedback of mTORC1 on upstream IRS2/PI3K signaling, and we demonstrate that this parallel signaling pathway is critical for induction of a subset of M2 markers. Tsc1-deficient macrophages fail to upregulate the M2 genes Pgc-1!, Arg-1, Fizz-1, and Mgl1 in addition to other M2 markers despite normal STAT6 signaling in response to IL-4. Consistent with downregulation of Pgc-1!, Tsc1-deficient macrophages also display defects in fatty acid metabolism and mitchochondrial biogenesis. Furthermore, LPS stimulation in Tsc-1 deficient macrophages leads to an enhanced inflammatory response with increased production of pro-inflammatory cytokines. We believe that Tsc1-deficient macrophages are a model of constitutive mTORC1 activity akin to obesity, where chronic nutrient excess leads to increases in mTORC1 activity, attenuation of IRS/PI3K/Akt signaling, and defective M2 polarization of macrophages in metabolic tissues.
45

Testicular macrophage regulation of Leydig cell development and function

Tsai, Yi-Ting January 2016 (has links)
The unique microenvironment structure of the testis affects the function of Leydig Cells (LCs) both physically and physiologically. The testicular macrophages are located adjacent to the LCs in the interstitial space and the two cell types share a close physiological and functional relationship. Macrophages first appear in the testis in prenatal life, and increase in number during both prenatal and postnatal development when they support the development and function of the testis. The dynamics of macrophage population expansion correlates with generation of the adult Leydig cell population in postnatal life. From these observations I hypothesise that testicular macrophage numbers have a consistent ratio to the number of LCs, and therefore manipulating testicular macrophage numbers may modulate LC number and testosterone (T) production by LCs. As such, manipulation of testicular macrophages represents a viable and novel mechanism by which LC function can be improved. To test this, markers for distinct macrophage populations in the testes were identified, namely c-fms-GFP, Mac2 and CD163. The number of either Mac2+ or CD163+ cell populations was determined at key stages throughout postnatal life, and the ratios of these cells to LC number were calculated at each age. This showed a consistent ratio between macrophages and LCs in the testis throughout postnatal life. The stimulatory effect of macrophages during LC development was then determined, by increasing the number of macrophages through cytokine treatment with recombinant CSF1-Fc. This model was then analysed for changes in testicular macrophage number, LC function and LC number. CSF1-Fc increased macrophage numbers in the developing testis. Macrophage number was increased following CSF1-Fc treatment at stem LC, progenitor LC and immature LC stages of LC development, and in adulthood. Importantly, increasing macrophage number during development led to early maturation of the LC population, suggesting macrophages may function as a driver of LC maturation. In adulthood, testicular macrophage numbers were reduced via treatment with an anti-CSF1 antibody to further determine the role of testicular macrophages in LC number and function. Whilst CD163+ macrophage number was reduced, no change in LH or T was observed. In contrast CSF1-Fc treatment induced an increase in macrophage number and LC number, with an elevated T level. Results suggest that macrophage support of steroidogenesis in adulthood is dispensable or can be compensated through LH/T feedback, but CSF1-Fc can contribute to LC function, LC number and T production through action at the level of the brain and the testis. Finally, to determine the potential clinical significance of increasing testicular macrophage support, experiments were completed on animals with pathological conditions: LC androgen receptor knockout mice (LCARKO) (LCs fail to fully mature) and ageing mice (cumulative free radical damage). Delivery of CSF1-Fc was observed to improve LC maturation in LCARKO mice, but failed to modulate LCs in ageing animals, suggesting CSF1-Fc may have clinical application in specific pathologies related to LC dysfunction. In summary, these studies further define the testicular macrophage population as important supporting cell types for LC development, function and maturation, and identifies possible mechanisms by which enhancing macrophage action can support or improve poor LC development and function.
46

Caractérisation d’une voie Immunomodulatrice impliquant l’arginase dans les Trypanosomoses / Characterization of an immunomodulatory pathway involving arginase in Trypanosomiasis

Nzoumbou-Boko, Romaric 30 October 2013 (has links)
Une nouvelle voie d’immunomodulation, l’induction de l’arginase par les trypanosomes chez leurs hôtes, a été identifiée et caractérisée. Pour éviter la réponse cytotoxique de l’activation « classique » M1 des macrophages et bénéficier de leur activation « alternative » M2, les parasites induisent l’arginase, qui produit la L-ornithine, indispensable à leur développement. Cette voie d’immunomodulation mise en évidence chez la souris infestée par son parasite naturel, Trypanosoma musculi, est également présente dans d’autres trypanosomoses, en particulier la trypanosomose humaine africaine (THA). Une augmentation de l’arginase, retrouvée dans le sérum de patients trypanosomés, se normalise après un traitement efficace. T. brucei gambiense, parasite de l’homme, induit l’arginase au niveau des macrophages murins et des leucocytes humains. T. lewisi, parasite du rat, induit également l’arginase. Au cours de leur longue coévolution avec leurs hôtes, les trypanosomes extracellulaires ont sélectionné un procédé favorisant leur croissance, l’induction de l’arginase, par des facteurs d’excrétion/sécrétion. Nous avons produit un anticorps monoclonal dirigé contre ce facteur inducteur. Il bloque l’induction de l’arginase par T. musculi in vitro et in vivo. Chez la souris infectée, son injection diminue considérablement la parasitémie. Il a permis l’identification du facteur inducteur, une kinésine orpheline. Cet anticorps, inhibant l’induction de l’arginase par différents trypanosomes, reconnaîtrait une région conservée de la kinésine induisant l’arginase. Cette kinésine se lie à des récepteurs de la membrane des macrophages. In vitro, l’addition de mannose à des co-cultures macrophages-parasites bloque l’induction de l’arginase et la multiplication des parasites. Chez la souris infestée par T. musculi, l’injection de mannose diminue la parasitémie, qui est également réduite chez les souris Mrc1-/-, KO pour le récepteur mannose. L’utilisation de molécules ciblant la voie inductrice de l’arginase et/ou ce récepteur peut représenter une nouvelle approche thérapeutique dans les trypanosomoses. / Arginase induction, a mechanism of immunomodulation elaborated by trypanosomes has been identified. To avoid cytotoxic classical M1 macrophage activation, trypanosomes induce alternative M2 macrophage activation, which leads to L-ornithine production, essential for parasite growth. This immunomodulation pathway has been evidenced in a natural murine trypanosomiasis provoked by Trypanosoma musculi. This mechanism is also evidenced in human African trypanosomiasis (HAT). An increase in serum arginase is measured in HAT patients. A return to normal values is obtained after an efficacious treatment. Trypanosoma brucei gambiense, the causative agent of HAT, induces arginase in mouse macrophages and human leucocytes. T. lewisi, a rat parasite, also induces macrophage arginase.During host-parasite co-evolution, extracellular trypanosomes have selected a growth promoting mechanism, macrophage arginase induction by excreted secreted factor (ESF). We have produced a monoclonal antibody which inhibits trypanosome-induced arginase. This antibody blocks in vitro and in vivo T. musculi-induced arginase. Its injection into infected mice provokes a decrease in parasite load. This monoclonal antibody has allowed the identification of an orphan kinesin as the arginase inducing factor. The arginase inducing region of kinesin seems conserved among extracellular trypanosomes. Kinesin binds to macrophage membrane receptors. In vitro, addition of mannose to macrophage-parasite cocultures blocks arginase induction and parasite multiplication. Mannose injection decreases parasite load in infected mice. Compared to WT mice, parasite load is highly reduced in infected Mrc1 -/- KO mice. In trypanosomiasis, molecules targeting arginase pathway and/or mannose receptor, highly conserved in evolution, might represent new therapeutic approaches.
47

The roles of macrophage migration inhibitory factor in human neuroblastoma development

Chan, Hiu-man, January 2006 (has links)
Thesis (Ph. D.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.
48

The Role of Ceramide in Oxidant-mediated Priming of Macrophages for LPS Signaling

Tawadros, Patrick 03 March 2010 (has links)
Introduction: Civilian trauma remains a significant health care problem in North American society. Hemorrhagic shock and resuscitation (S/R) have been shown to prime the immune system for an exaggerated response to subsequent otherwise innocuous inflammatory stimuli such as lipopolysaccharide (LPS), resulting in multiple organ failure or death. Using a rodent model of lung injury, we previously demonstrated that antecedent S/R leads to augmented LPS-induced lung injury by way of heightened NF-κB nuclear translocation, resulting in increased elaboration of pro-inflammatory cytokines in alveolar macrophages. Further studies revealed that oxidative stress generated during S/R is responsible for this priming phenomenon. Our group recently identified two significant alterations to LPS signaling under oxidative stress conditions in macrophages: 1) the rapid recruitment of the LPS receptor Toll-like receptor 4 (TLR4) to membrane lipid rafts, and 2) the reprogramming of LPS signaling to a Src-dependent pathway involving phosphatidylinositol 3-kinase (PI3K). Major Objective and Hypothesis: The objective of this thesis is to elucidate the molecular mechanisms underlying the augmented cellular responsiveness observed in macrophages following oxidative stress. The central hypothesis is that oxidative stress regulates LPS signaling by altering the activation and assembly of TLR4 receptor signaling components through generation of the lipid ceramide. Summary of Findings: In the first paper, we demonstrate that the antioxidant stilbazulenyl nitrone (STAZN), a novel second-generation azulenyl nitrone, is protective in a rodent two-hit model of lung injury involving hemorrhagic S/R and subsequent intra-tracheal LPS injection. Resultant oxidative stress and lung injury in vivo were significantly reduced by STAZN following S/R and LPS. In the second paper, we explore the mechanism underlying oxidant-induced surface up-regulation of TLR4 in macrophages. Using immunofluorescence microscopy and flow cytometry techniques, hydrogen peroxide in vitro and hemorrhagic S/R in vivo are shown to induce TLR4 translocation in macrophages in a ceramide and Src-dependent manner, and the enzyme acid sphingomyelinase (ASM) is shown to mediate ceramide generation. In the third paper, the role of ceramide in oxidant-induced macrophage priming for LPS signaling is investigated. Ceramide generation via ASM is shown to have a prominent upstream role in oxidant activation of the PI3K/Akt pathway via Src kinases in macrophages. Furthermore, oxidative stress is shown to reprogram LPS signaling to a ceramide dependent pathway. Conclusion: Together, these findings highlight the role of oxidative stress in mediating augmented cellular responsiveness following S/R, and describe the role of ceramide as a central upstream mediator of oxidant priming in macrophages. The hierarchy of signaling molecules and interactions described herein represent novel targets for modulating oxidative stress in the treatment of critical illness and organ injury.
49

Mechanisms of 7,8-dihydroneopterin protection of macrophages from cytotoxicity

Shchepetkina, Anastasia January 2013 (has links)
Gamma-interferon stimulates human macrophages to produce of 7,8-dihydroneopterin (7,8-NP). 7,8-NP and its oxidation product neopterin are excellent inflammatory markers for a variety of chronic conditions, including atherosclerosis. The biological significance of 7,8-NP in atherosclerosis is not fully understood, but 7,8-NP has been shown to protect macrophage cells from oxidised low density lipoprotein (oxLDL). Cellular accumulation of oxLDL-derived lipids and oxLDL-induced cytotoxicity are major drivers of atherosclerotic plaque progression. This thesis investigated the mechanisms of 7,8-NP-mediated protection against oxLDL-induced damage to macrophage cells. The research assessed the relative contribution of the previously identifyed antioxidant capacity of 7,8-NP and its ability to down-regulate oxLDL uptake. OxLDL cytotoxicity was characterised by high intracellular oxidative stress within the first 12 hours of exposure, which was critical to oxLDL toxicity. Exogenously added 7,8-NP effectively scavenged the intracellular oxidants generated in response to oxLDL, shown by the oxidation of 7,8-NP to neopterin. The ability of 7,8-NP to alleviate oxidative stress during the critical time-frame of acute toxicity was the primary mechanism of protection. 7,8-NP was also found to down-regulate the levels of intracellular oxysterol esters in oxLDL-treated macrophages. This decrease was associated with the reduction of CD36 scavenger receptor protein and mRNA expression. The late onset of these processes in the second half of the 24 hour incubation highlighted their potential role in foam cell formation. Research indicated that 7,8-NP may play a role in the reverse cholesterol transport in these cholesterol ester-loaded cells. The CD36 down-regulation by 7,8-NP did not protect macrophages from acute oxLDL cytotoxicity. This research reveals novel detail about the mechanism of 7,8-NP protection of macrophages from cytotoxic effects of oxLDL. It is suggested that 7,8-NP may protect macrophage cells in the atherosclerotic plaques by scavenging ROS produced during acute cytotoxicity and alleviate oxysterol ester accumulation, thus stabilising macrophage cells during chronic oxLDL exposure.
50

Dietary lipids and inflammation : chylomicron remnants suppress pro-inflammatory pathways and activate antioxidant defence mechanisms in human macrophages

Di Maggio, Paula January 2013 (has links)
No description available.

Page generated in 0.0446 seconds