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Yoshimasa Yamamoto

Bio: Yoshimasa Yamamoto is an academic researcher from Osaka University. The author has contributed to research in topics: Legionella pneumophila & Cytokine. The author has an hindex of 33, co-authored 145 publications receiving 3977 citations. Previous affiliations of Yoshimasa Yamamoto include Japan International Cooperation Agency & National Institutes of Health.


Papers
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Journal ArticleDOI
TL;DR: Results revealed that nAChRs, the major exogenous ligands of which are nicotine, are involved in the regulation of macrophage immune function by nicotine and may contribute to the cigarette-induced risk factors for respiratory infections in smokers.
Abstract: Although nicotine is thought to be one of the major immunomodulatory components of cigarette smoking, how nicotine alters the host defense of the lung and, in particular, immune responses of alveolar macrophages, which are critical effector cells in the lung defense to infection, is poorly understood. Nicotinic acetylcholine receptors (nAChRs) are the receptor for nicotine and may be involved in the modulation of macrophage function by nicotine. In this study, therefore, nicotine-induced suppression of antimicrobial activity and cytokine responses of alveolar macrophages mediated by nAChRs to Legionella pneumophila , a causative agent for pneumonia, were examined. The murine MH-S alveolar macrophage cell line cells expressed the messages for α4 and β2 subunits of nAChRs, but not α7 subunits, determined by RT-PCR. The nicotine treatment of MH-S alveolar macrophages after infection with L. pneumophila significantly enhanced the replication of bacteria in the macrophages and selectively down-regulated the production of IL-6, IL-12, and TNF-α, but not IL-10, induced by infection. These effects were completely blocked by a nonselective antagonist, d -tubocurarine, for nAChRs, but not by a selective antagonist, α-bungarotoxin, for α7-nAChRs. Furthermore, the stimulation of nAChRs with another agonist, 1,1-dimethyl-4-phenylpiperazinium iodide, showed the same effects, which were blocked by the antagonist d -tubocurarine, on the bacterial replication and cytokine regulation with that of nicotine. Thus, the results revealed that nAChRs, the major exogenous ligands of which are nicotine, are involved in the regulation of macrophage immune function by nicotine and may contribute to the cigarette-induced risk factors for respiratory infections in smokers.

244 citations

Journal ArticleDOI
TL;DR: The data suggest that, as with other intracellular bacteria, macrophages may serve a pivotal role in the early stages of Legionella infection and further suggest that the A/J mouse represents a useful animal model for the study of Legionnaires' disease and immunity.
Abstract: Legionella pneumophila is a facultative intracellular bacterium which readily grows in cultures of guinea pig and human mononuclear phagocytes. In this report, we demonstrate that the Legionella sp. also grows in thioglycolate-elicited macrophages obtained from A/J mice but not in cells from other mouse strains tested, such as BDF1, DBA/2, C3H/HeN, C57BL/6, and BALB/c. Growth of Listeria monocytogenes and interleukin-1 production in A/J mice were similar to their growth and production in other strains tested, and the growth of Staphylococcus epidermidis was restricted by A/J macrophages. This finding suggests that although A/J macrophages share functional capabilities with cells from other mouse strains, they differ in growth restriction capacity for the Legionella sp. Resident macrophages were less permissive than were thioglycolate-elicited cells in that resident cells from A/J mice failed to support the growth of Legionella pneumophila. Also, resident cells from BDF1 mice rapidly eliminated the bacteria, rather than merely restricting growth. This finding was also observed in in vivo studies in which thioglycolate pretreatment of mice resulted in the enhanced recovery of viable bacteria from the peritoneal cavity of mice infected intraperitoneally. Higher numbers of bacteria were obtained from A/J mice and, in addition, this strain was more susceptible to the lethal effects of Legionella infection. These data suggest that, as with other intracellular bacteria, macrophages may serve a pivotal role in the early stages of Legionella infection and further suggest that the A/J mouse represents a useful animal model for the study of Legionella infection and immunity.

197 citations

Journal ArticleDOI
TL;DR: Results indicate that selected cytokine responses of macrophages to C. albicans are mediated by MR, while some chemokine responses may be mediated by other receptors.
Abstract: The production of chemotactic cytokines (chemokines) and other cytokines by macrophages in response to fungal infection is thought to be critical during the course of candidiasis. However, the mechanism of cytokine synthesis by macrophages in response to fungi is not well understood. Therefore, the response of macrophages to Candida albicans was examined in terms of receptor-mediated chemokine and other cytokine mRNA induction. Attachment of C. albicans to murine thioglycollate-elicited peritoneal macrophages induced increased mRNA levels of the cytokines interleukin-1beta (IL-1beta), IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF) and the chemokines macrophage inflammatory protein 1beta (MIP-1beta), MIP-2, and KC (a member of the platelet factor 4 neutrophil chemoattractant family), as determined by quantitative reverse transcription-PCR. However, treatment of macrophages with alpha-methyl-D-mannoside significantly reduced the cytokine GM-CSF response to C. albicans but did not affect the chemokine MIP-2 response. Antisense oligodeoxynucleotide (ODN) to mannose receptor (MR) mRNA inhibited the expression and function of MR in macrophages as determined by Western blot analysis and 125I-labeled mannose-bovine serum albumin (BSA) binding, and also inhibited the elevation of cytokine IL-1beta, IL-6, and GM-CSF mRNA levels induced by C. albicans attachment. Elevation of chemokine MIP-1beta, MIP-2, and KC mRNA levels induced by C. albicans was not affected in macrophages whose MR expression was suppressed by antisense ODN treatment. Furthermore, IL-4 treatment of macrophages, which up-regulated MR expression as determined by Western blot analysis and fluorescein isothiocyanate-labeled mannose-BSA uptake, enhanced the level of cytokine GM-CSF mRNA induced by C. albicans but not the level of the chemokine MIP-2 mRNA. These results indicate that selected cytokine responses of macrophages to C. albicans are mediated by MR, while some chemokine responses may be mediated by other receptors.

178 citations

Journal ArticleDOI
TL;DR: Treatment of macrophage cultures with purified bacterial hsp increased the steady-state levels of cytokine mRNA for interleukin-1 alpha (IL-1alpha), IL-1 beta, IL-6, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor as well as supernatant IL- 1 secretion, suggesting that bacterial hSp might modulate immunity by rapidly and directly increasing cytokine production in macrophages.
Abstract: Bacterial heat shock proteins (hsp) have been shown to be important immunogens stimulating both T cells and B cells. However, little is known concerning the direct interactions between hsp and macrophages. In this study, we demonstrated that treatment of macrophage cultures with purified bacterial hsp, including Legionella pneumophila hsp60, Escherichia coli GroEL, Mycobacterium tuberculosis hsp70, Mycobacterium leprae hsp65, and Mycobacterium bovis BCG hsp65, increased the steady-state levels of cytokine mRNA for interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor as well as supernatant IL-1 secretion. This effect was shown not to be due to contamination of the hsp preparations with bacterial lipopolysaccharide. However, not all hsp induced cytokines; M. tuberculosis hsp10 showed minimal activity in our study. These results suggest that bacterial hsp might modulate immunity by rapidly and directly increasing cytokine production in macrophages.

172 citations

Journal ArticleDOI
TL;DR: Current studies concerning detection of Chlamydia pneumoniae in CSF obtained from patients with multiple sclerosis by using PCR provide a good example for discussion of use of the PCR assay in diagnosis.
Abstract: The PCR is the most sensitive of the existing rapid methods to detect microbial pathogens in clinical specimens. In particular, when specific pathogens that are difficult to culture in vitro or require a long cultivation period are expected to be present in specimens, the diagnostic value of PCR is known to be significant. However, the application of PCR to clinical specimens has many potential pitfalls due to the susceptibility of PCR to inhibitors, contamination and experimental conditions. For instance, it is known that the sensitivity and specificity of a PCR assay is dependent on target genes, primer sequences, PCR techniques, DNA extraction procedures, and PCR product detection methods. Even though there are many publications concerning basic protocols of a PCR assay, including DNA extraction and preparation as well as the amplification and detection of amplicons, PCR detection of bacteria in clinical specimens such as cerebrospinal fluid (CSF) has not yet been reviewed. Since a variety of clinical specimens, such as blood, urine, sputum, CSF and others, vary in regard to the nature of the content and amount available, careful design of the PCR assay for each specific specimen before a PCR application is conducted is essential. In particular, a diagnosis based on detection of a few bacteria in clinical specimens by using PCR must be carefully evaluated technically as well as microbiologically. In this regard, current studies concerning detection of Chlamydia pneumoniae in CSF obtained from patients with multiple sclerosis (MS) by using PCR provide a good example for discussion of use of the PCR assay in diagnosis. Because C. pneumoniae is difficult to culture in vitro, often low numbers of bacteria may be detected in the CSF of patients with chronic neurological diseases by PCR. Therefore, in this review general PCR protocols for detection of bacteria in clinical specimens, as well as a specific example of using PCR for detection of C. pneumoniae in CSF, will be discussed.

169 citations


Cited by
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TL;DR: Macrophages also play an important role in the recognition and clearance of apoptotic cells; a notable feature of this process is the absence of an inflammatory response.
Abstract: Phagocytosis of pathogens by macrophages initiates the innate immune response, which in turn orchestrates the adaptive response. In order to discriminate between infectious agents and self, macrophages have evolved a restricted number of phagocytic receptors, like the mannose receptor, that recognize conserved motifs on pathogens. Pathogens are also phagocytosed by complement receptors after relatively nonspecific opsonization with complement and by Fc receptors after specific opsonization with antibodies. All these receptors induce rearrangements in the actin cytoskeleton that lead to the internalization of the particle. However, important differences in the molecular mechanisms underlying phagocytosis by different receptors are now being appreciated. These include differences in the cytoskeletal elements that mediate ingestion, differences in vacuole maturation, and differences in inflammatory responses. Infectious agents, such as M. tuberculosis, Legionella pneumophila, and Salmonella typhimurium, enter macrophages via heterogeneous pathways and modify vacuolar maturation in a manner that favors their survival. Macrophages also play an important role in the recognition and clearance of apoptotic cells; a notable feature of this process is the absence of an inflammatory response.

2,774 citations

Journal ArticleDOI
TL;DR: It is considered premature to rename cannabinoid receptors after an endogenous agonist as is recommended by the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification, because pharmacological evidence for the existence of additional types of cannabinoid receptor is emerging and other kinds of supporting evidence are still lacking.
Abstract: Two types of cannabinoid receptor have been discovered so far, CB(1) (2.1: CBD:1:CB1:), cloned in 1990, and CB(2) (2.1:CBD:2:CB2:), cloned in 1993. Distinction between these receptors is based on differences in their predicted amino acid sequence, signaling mechanisms, tissue distribution, and sensitivity to certain potent agonists and antagonists that show marked selectivity for one or the other receptor type. Cannabinoid receptors CB(1) and CB(2) exhibit 48% amino acid sequence identity. Both receptor types are coupled through G proteins to adenylyl cyclase and mitogen-activated protein kinase. CB(1) receptors are also coupled through G proteins to several types of calcium and potassium channels. These receptors exist primarily on central and peripheral neurons, one of their functions being to inhibit neurotransmitter release. Indeed, endogenous CB(1) agonists probably serve as retrograde synaptic messengers. CB(2) receptors are present mainly on immune cells. Such cells also express CB(1) receptors, albeit to a lesser extent, with both receptor types exerting a broad spectrum of immune effects that includes modulation of cytokine release. Of several endogenous agonists for cannabinoid receptors identified thus far, the most notable are arachidonoylethanolamide, 2-arachidonoylglycerol, and 2-arachidonylglyceryl ether. It is unclear whether these eicosanoid molecules are the only, or primary, endogenous agonists. Hence, we consider it premature to rename cannabinoid receptors after an endogenous agonist as is recommended by the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. Although pharmacological evidence for the existence of additional types of cannabinoid receptor is emerging, other kinds of supporting evidence are still lacking.

2,619 citations

Journal ArticleDOI
TL;DR: This review focuses on the biology of A. fumigatus, one of the most ubiquitous of the airborne saprophytic fungi, and the diseases it causes, and discusses discussions of genomic and molecular characterization of the organism.
Abstract: Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic fungi. Humans and animals constantly inhale numerous conidia of this fungus. The conidia are normally eliminated in the immunocompetent host by innate immune mechanisms, and aspergilloma and allergic bronchopulmonary aspergillosis, uncommon clinical syndromes, are the only infections observed in such hosts. Thus, A. fumigatus was considered for years to be a weak pathogen. With increases in the number of immunosuppressed patients, however, there has been a dramatic increase in severe and usually fatal invasive aspergillosis, now the most common mold infection worldwide. In this review, the focus is on the biology of A. fumigatus and the diseases it causes. Included are discussions of (i) genomic and molecular characterization of the organism, (ii) clinical and laboratory methods available for the diagnosis of aspergillosis in immunocompetent and immunocompromised hosts, (iii) identification of host and fungal factors that play a role in the establishment of the fungus in vivo, and (iv) problems associated with antifungal therapy.

2,083 citations

01 Jan 2009
TL;DR: A review of the biology of Aspergillus fumigatus and the diseases it causes can be found in this article, where the authors discuss genomic and molecular characterization of the organism, clinical and laboratory methods available for the diagnosis of aspergillosis in immunocompetent and immunOCompromised hosts, identification of host and fungal factors that play a role in the establishment of the fungus in vivo, and problems associated with antifungal therapy.
Abstract: SUMMARY Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic fungi. Humans and animals constantly inhale numerous conidia of this fungus. The conidia are normally eliminated in the immunocompetent host by innate immune mechanisms, and aspergilloma and allergic bronchopulmonary aspergillosis, uncommon clinical syndromes, are the only infections observed in such hosts. Thus, A. fumigatus was considered for years to be a weak pathogen. With increases in the number of immunosuppressed patients, however, there has been a dramatic increase in severe and usually fatal invasive aspergillosis, now the most common mold infection worldwide. In this review, the focus is on the biology of A. fumigatus and the diseases it causes. Included are discussions of (i) genomic and molecular characterization of the organism, (ii) clinical and laboratory methods available for the diagnosis of aspergillosis in immunocompetent and immunocompromised hosts, (iii) identification of host and fungal factors that play a role in the establishment of the fungus in vivo, and (iv) problems associated with antifungal therapy.

2,040 citations

Journal ArticleDOI
TL;DR: Large amounts of variation among regions are observed among regions-more than half the world's population is infected, which can be used in development of customized strategies for the global eradication.

1,763 citations