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  • 2000-2004  (4)
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  • 1
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In parallel with the Th1/Th2 dichotomy, macrophages are capable of developing into functionally and molecularly distinct subpopulations, due to differences in, for example cytokine environment and pathological conditions. While the best-studied, classically activated macrophage is induced by type I stimuli such as IFN-γ, a type II cytokine environment antagonizes the classical activation of macrophages and is capable of alternatively activating macrophages. However, molecular markers associated with these type II cytokine-dependent, alternatively activated macrophages remain scarce. Besides the earlier documented markers macrophage mannose receptor and arginase 1, we recently demonstrated that murine alternatively activated macrophages are characterized by increased expression of FIZZ1 and Ym. We now report that expression of the two members of the mouse macrophage galactose-type C-type lectin gene family, termed mMGL1 and mMGL2, is induced in diverse populations of alternatively activated macrophages, including peritoneal macrophages elicited during infection with the protozoan Trypanosoma brucei or the Helminth Taenia crassiceps, and alveolar macrophages elicited in a mouse model of allergic asthma. We also demonstrate that, in vitro, interleukin-4 and interleukin-13 upregulate mMGL1 and mMGL2 expression and that, in vivo, induction of mMGL1 and mMGL2 is dependent on interleukin-4 receptor signalling. Moreover, we show that regulation of MGL expression is similar in human monocytes and monocyte-derived macrophages. Hence, macrophage galactose-type C-type lectins represent novel markers for both murine and human alternatively activated macrophages; thus, paving the way for further characterization of the phenotype of macrophages occurring in Th2 conditions.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Science Ltd/Inc.
    Scandinavian journal of immunology 59 (2004), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We previously reported that in mice with large progressing T-cell lymphoma tumours, dysfunctions in the antitumour CTL activity occur, associated with an accumulation of splenic arginase-producing myeloid suppressor cells (MSCs). In this study, we first demonstrate that both the presence and the activation state of these MSC depends on tumour evolution. While in tumour regressors hardly any arginase-producing MSC can be found, both the amount and the arginase activity of this population expands from early over late progressors. This gradual induction of MSCs is paralleled by an increasing suppression of CTL activity and Th1, but not Th2, cytokine production. Upon analysing the molecular repertoire of MSC in vitro, we found, besides arginase1, a well-established marker for alternatively activated myeloid cells or M2, a strong upregulation of FIZZ1 and Ym, two additional recently identified markers for M2. Further evaluation of molecular markers by microarray analysis in MSC yielded genes involved in wound healing (e.g. coagulation factor XIIIa), anti-inflammation (e.g. selenoprotein P), immunomodulation (e.g. PD-L2) and fat and sugar metabolism (e.g. leptin receptor). Of note, many of these genes are regulated by type 2 cytokines (IL-4, IL-13 and IL-10) and are therefore rather M2 associated. Overall, our data provide new markers for MSC in cancer and further establish their M2 activation state.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Coelomic cytolytic factor (CCF) is a 42 kDa invertebrate pattern recognition molecule isolated from the coelomic fluid of the earthworm Eisenia foetida (Oligochaeta, Annelida). CCF displays a number of similarities with the mammalian cytokine tumour necrosis factor-α (TNF-α) as a result of a shared N,N′-diacetylchitobiose lectin-like domain. However, these similarities are solely functional and are not based on any (DNA or amino acid) sequence homology, thus suggesting a form of convergent evolution. In particular, the lectin-like domain of TNF-α has been shown to induce membrane depolarization in various mammalian cell types, through interactions with endogenous amiloride-sensitive ion channels. This nonreceptor-mediated activity of TNF-α has been reported to be involved in the resorption of oedema. Likewise, the lectin-like domain of CCF also induces membrane depolarization in mammalian cells. Here, we show that CCF appears to be able to induce oedema resorption in an alveolar epithelial cell line through its lectin-like domain. This lectin-like domain of CCF interacts (directly or indirectly) with endogenous sodium and/or chloride channels, and not potassium channels, on mammalian cells. Additionally, we suggest that the JNK/SAPK and Erk1/2 pathways are involved in CCF-induced macrophage activation. These results further establish the functional analogy between an invertebrate pattern recognition molecule and a mammalian cytokine and, from a more applied point of view, suggest the possibility of utilizing CCF in the treatment of oedema.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Science Ltd/Inc.
    Scandinavian journal of immunology 59 (2004), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Immunity against tuberculosis (TB), caused by Mycobacterium tuberculosis, depends largely on activation and maintenance of strong cell-mediated immune responses involving both CD4+ and CD8+ T cells and the ability to respond with Th1-type cytokines, particularly IFN-γ. Recent studies suggested that BCG, the only licensed vaccine against M. tuberculosis, may fail to induce T-cell responses in the lung mucosa and may therefore not protect against pulmonary TB. A decrease in TB mortality may be achieved by enhancing immunity in the lung. The present study evaluated the induction of antigen-specific immunity in the lung by intranasal (i.n.) delivery of the lipoprotein I (OprI) from Pseudomonas aeruginosa. OprI has shown to be a Toll-like receptor 2/4 agonist that, when given subcutaneously, induces Type-1 immune responses against heterologous antigens. Here, a fusion of OprI to Ag85A of Mtb (OprI-Ag85A) was used as a subunit vaccine in homologous prime-boost immunizations. In addition, OprI-Ag85A was combined with an Ag85A-encoding DNA vaccine (Ag85A DNA) or with BCG in heterologous prime-boost vaccinations. Intranasal and parenteral delivery with OprI-Ag85A elicited comparable T-cell responses in the spleen; in addition, i.n. delivery elicited specific T-cell responses in the lung lymph nodes (LLNs). Intramuscular delivery of Ag85A DNA induced significant systemic Th1 immune responses. Intranasal boosting with OprI-Ag85A enhanced this response and in addition induced an antigen-specific IFN-γ response in LLN. OprI may therefore be an efficient adjuvant for mucosal boosting. We continue to evaluate the protection induced by OprI-based prime-boost vaccinations against pulmonary TB. Results on the immunogenicity and protection against intravenous Mtb H37Rv infection will be presented.
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