Biomedical subjects

M Miyamasu

Publications and source records attributed to M Miyamasu.

26 records · Page 2Linked to original sources

PubMed1997

Eotaxin is a potent chemotaxin for human basophils.

We studied the effect of eotaxin, a novel eosinophil-active CC chemokine with high target cell specificity, on human basophils. Eotaxin induced higher levels of chemotactic response with a lower ED50 compared with RANTES in basophils; half-maximal migration occurred at a concentration of approximately 3 nM. On the other hand, it exerted only a marginal effect on either histamine release or leukotriene C4 generation. In addition, nested PCR amplification experiments revealed the expression of CC CKR3, a putative receptor for eotaxin, on basophils. Since accumulation of both basophils and eosinophils is an important aspect of allergic inflammation, eotaxin potentially plays a pathogenic role in allergic disorders by inducing migration of both of these cell types.

Basophils↗

PubMed1997

Expression and regulation of monocyte chemoattractant protein-1 by human eosinophils.

Several recent studies have identified eosinophils as a cellular source of various cytokines, indicating that eosinophils play not only an effector role, but also a regulatory role within the allergic inflammatory cell network. In this study, we demonstrate that eosinophils can generate and secrete monocyte chemoattractant protein-1 (MCP-1), a prototype of C-C chemokines. Eosinophils generated immunoreactive MCP-1 in response to such diverse stimuli as C5a, formyl-methionyl-leucyl-phenylalanine (FMLP) and ionomycin, but MCP-1 production was not induced by interleukin (IL)-1 or tumor necrosis factor-alpha. C5a- and FMLP-induced eosinophil MCP-1 production was absolutely dependent on pretreatment with cytochalasin B. Eosinophils elaborated significantly more MCP-1 than neutrophils. Immunoreactive MCP-1 was detected at 6 h of incubation with C5a or FMLP. Expression of MCP-1 mRNA reached a maximum within the first 3 h after stimulation and then declined rapidly to a very low and stable level by 18 h. Pretreatment with IL-5 markedly amplified C5a-induced MCP-1 production, and the enhancement occurred at the pretranslational level. Eosinophil-active chemokines such as eotaxin failed to induce MCP-1 generation, even when eosinophils were primed by IL-5. Since MCP-1 exerts a potent histamine-releasing effect on human basophils, our results indicate that eosinophils may regulate basophil mediator release with possible consequent contribution to the pathogenesis of allergic inflammation via a paracrine mechanism.

Chemokine CCL2↗

PubMed1997

Eosinophilopoietic factors prime eosinophils for increased interleukin-8 generation.

Recent studies have identified eosinophils as a cellular of various cytokines, indicating that eosinophils play not only an effector role but also a regulatory role within the allergic inflammatory cell network. Because eosinophilopoietic factors are known to stimulate various functions of eosinophils, we examined the effect of interleukin (IL)-5 on chemoattractant-induced IL-8 generation from eosinophils. Although IL-5 alone induced little or no IL-8 production from eosinophils, short-term preincubation with IL-5 markedly enhanced the eosinophil IL-8 generation caused by C5a plus cytochalasin B (CB). IL-3 also potentiated C5a-induced IL-8 generation. Both factors were active at picomolar concentrations. Furthermore, competitive polymerase chain reaction (PCR) experiments revealed that the enhancement occurred at the pretranslational level. Since eosinophils in allergic inflammation are believed to be activated by these eosinophilopoietic factors, eosinophil-derived cytokines may play more important roles in the allergic inflammatory cell network than has been previously supposed.

Cells, Cultured↗

PubMed1997

Regulation of the function of eosinophils and basophils.

Both eosinophils and basophils play active pathogenic roles in the inflammation associated with allergic disorders. Both types of cells share a majority of their cell surface structures, and because of these common surface molecules, both cells can be stimulated with a single ligand simultaneously. The growth of both types of cells is controlled by IL-3, GM-CSF, and IL-5. All three growth factors are also capable of priming both eosinophils and basophils for enhanced biological functions, such as increased mediator release and prolonged survival. Both cells express beta 2 integrins, and in contrast to neutrophils, they also express several beta 1 integrins. Ligation of these adhesion molecules also transduces the intracellular signal leading to regulation of the cellular functions. In this review, we briefly describe the effects of various ligands of surface receptors and several pharmacological compounds on the functions of human eosinophils and basophils.

Animals↗

PubMed1995

Chemotactic agonists induce cytokine generation in eosinophils.

Recent studies have shown that eosinophils are capable of generating and releasing cytokines, providing a novel biologic aspect of eosinophils for regulating allergic inflammation by an autocrine or paracrine mechanism. Eosinophils synthesize various cytokines; however, the physiologic stimuli that trigger eosinophils to generate cytokines have not been fully elucidated. We examined the effect of chemotactic agonists on eosinophil cytokine generation by employing the determination of IL-8 as the main parameter. Both C5a and FMLP stimulated eosinophils to release IL-8, whereas platelet-activating factor and C-C chemokines did not exert any significant effects. On a molar basis, C5a was two orders of magnitude more potent than FMLP. The generation of IL-8 by chemoattractants was absolutely dependent on the presence of cytochalasin B. Pertussis toxin completely attenuated C5a- and FMLP-induced IL-8 production, indicating the involvement of pertussis toxin-sensitive G-proteins in the signal-transduction process leading to these responses. Experiments of in situ hybridization and PCR amplification revealed that both C5a and FMLP promoted eosinophil IL-8 production through transcriptional gene activation. Pyrrolidine dithiocarbamate completely abrogated chemoattractant-induced IL-8 production, indicating the involvement of NF-kappa B in the cytoplasmic/nuclear signal-transduction process. Furthermore, chemoattractant-induced cytokine production was not limited to IL-8; C5a and FMLP but not platelet-activating factor induced significant secretion of granulocyte-macrophage-CSF from eosinophils. These results indicate that C5a and FMLP stimulate eosinophils to elaborate cytokines, which could be an important mechanism in the regulation of allergic inflammation.

Base Sequence↗

PubMed1995

Induction of eosinophil cytokine generation by chemoattractants.

Recent studies have shown that eosinophils are capable of generating and releasing cytokines, illustrating a novel biologic aspect of eosinophils in regulating allergic inflammation by either autocrine or paracrine mechanisms. The effect of chemotactic agonists on eosinophil cytokine generation was examined by determination of interleukin-8 (IL-8) as a main parameter. Both complement C5a and N-formyl-methionyl-leucyl-phenylalanine (FMLP) stimulated eosinophils to release IL-8, but platelet activating factor (PAF) did not exert any significant effects. The generation of IL-8 by chemoattractants was absolutely dependent on the presence of cytochalasin B. Pertussis toxin completely attenuated C5a- and FMLP-induced IL-8 production, indicating the involvement of pertussis toxin-sensitive G proteins in the signal transduction process. In situ hybridization showed that both C5a and FMLP promoted eosinophil IL-8 production via transcriptional gene activation. Furthermore, C5a and FMLP, but not PAF, induced significant secretion of granulocyte-macrophage colony-stimulating factor from eosinophils. These results indicate that C5a and FMLP stimulate eosinophils to elaborate cytokines, which could be an important mechanism in the regulation of allergic inflammation.

Actin Cytoskeleton↗

PubMed1993

Modulation of human basophil histamine release by insulin-like growth factors.

Several lines of evidence indicate that basophils play an active pathogenic role in the late-phase reaction. Inasmuch as various cytokines are produced locally by activated cells of the immune system during late-phase reaction, "priming" of basophils by cytokines has become an area of active study over the last few years. We studied the effect of insulin-like growth factor (IGF)-I, shown to be active on immature and mature hemopoietic cells, on histamine release from human basophils. IGF-I enhanced histamine release initiated by anti-IgE, calcium ionophore A23187, and phorbol ester in a dose-dependent fashion (ED50: 300-600 pM), although IGF-I had little or no effect on the release caused by FMLP and C5a. The priming effect of IGF-I took place rapidly and reached plateau levels in 15 min. IGF-II and insulin, both of which have high amino acid sequence homology with IGF-I, also primed basophils. The order of enhancing potencies was IGF-I > IGF-II > insulin; IGF-I was 10-fold more potent than IGF-II and 250-fold more potent than insulin. Although specific receptors for each factor have been identified, blocking experiments using a mAb against IGF-I receptor showed almost complete abolishment of the enhancing effect of these factors, indicating that the enhancing effect is exhibited via the IGF-I receptor. Inasmuch as IGF-I has been shown to be produced by alveolar macrophages, fibroblasts, and nasal polyps, these results indicate that IGF may regulate allergic reactions in vivo by enhancing histamine release from basophils.

Basophils↗

PubMedDate not supplied

Study of chemobiological reactions. 1. Selectivity of aromatic amino compounds and saccharides in glycosylation reactions.

The reactivities between saccharides and primary amino compounds were studied by liquid chromatography on an amino-bonded column and by measurement of the reaction rates of aromatic amines with saccharides. The recoveries from the column and the reaction rates were correlated with their physicochemical properties calculated by the CAChe program. The reactivities between amines and saccharides correlated well with their hydrogen bonding energies calculated by molecular mechanics.

Amines↗