Biomedical subjects

C Ra

Publications and source records attributed to C Ra.

At least 91 records · Page 5Linked to original sources

PubMed1996

FcR gamma-chain is essential for both surface expression and function of human Fc gamma RI (CD64) in vivo.

Most Ig receptors exist as hetero-oligomeric complexes with separate ligand binding (alpha) and signal transducing (beta, gamma, or zeta) subunits. For Fc gamma RIIIa and Fc epsilon RI, association with the FcR gamma-chain is essential for surface expression. However, the human high affinity IgG receptor, hFc gamma RI, was found to be surface-expressed by itself in transient transfection models. We have now analyzed the integrity of hFc gamma RI expression in more detail in stable transfectants. In vitro we noted that, in the absence of FcR gamma-chain, surface expression of hFc gamma RI rapidly declined to background levels, in both IIA1.6 B cells and NIH3T3 fibroblasts. The effect of FcR gamma-chain on hFc gamma RI surface expression in vivo was evaluated by using two newly generated transgenic mouse lines, selectively expressing hFc gamma RI on myeloid cells. These transgenic mice were crossed with FcR gamma-chain-deficient mice. Analysis of blood monocytes and peritoneal macrophages showed that surface expression of hFc gamma RI was reduced by approximately 80%. The remaining approximately 20% of receptors were still capable of binding IgG-opsonized RBC, suggesting FcR gamma-chain not to be critical for hFc gamma RI ligand-binding capacity. Importantly, however, hFc gamma RI signaling capacity was lost in FcR gamma-chain-deficient cells. No phagocytosis could be observed using either ligand sensitized (EA-IgG2a) or CD64-targeted erythrocytes (using a bispecific antibody) in both hFc gamma RI transgenic lines. This documents the FcR gamma-chain to be indispensable for both surface membrane expression and function of human Fc gamma RI in vivo.

Animals↗

PubMed1996

Heterogeneity of mast cells and T cells in the nasal mucosa.

Allergic diseases like atopic rhinitis, bronchial asthma, and urticaria are prevalent and on the rise. The need to better understand the pathophysiology of these diseases is therefore crucial to the development of newer and more effective modes of treatment. We hypothesized that in inflammatory diseases like allergic rhinitis and asthma characterized by profound local clinical manifestations and inflammation of the relevant mucosae, the most important immunopathological findings must occur locally. Although studies on the cellular elements and mediators in the peripheral blood compartment may provide useful information, they may not accurately reflect events occurring within the target organ itself. Even in the normal mucosa there is a resident population of lymphocytes and mast cells. Taking perennial allergic rhinitis (PAR) and chronic infective rhinitis (CIR) as representative chronic airway inflammatory diseases we investigated the phenotypic and functional characteristics of mast cells and lymphocytes in the nasal mucosa of patients with PAR and CIR during the natural course of the disease. We further compared the characteristics of lymphocytes in the nasal mucosa with that in the peripheral blood compartment. Our results demonstrated heterogeneity of mast cells and T cells in the nasal mucosa. Furthermore, the mucosal changes at the site of allergic inflammation were characterized by an increase in the proportion of CD4+ CD45RO+ T cells (memory cells); oligoclonal expansion and activation of V gamma 1/V delta 1+ T cells; an increased number of Fc epsilon RI+ cells; an increased proportion of TH2-type cytokine expressing mast cells and lymphocytes and of very late antigen-4 and very late antigen-5 expressing nasal mast cells, independent of alterations in CIR; and autologous peripheral blood. These findings strongly suggest heterogeneity of lymphocytes and mast cells in the nasal mucosa based on the underlying inflammatory disease, and compartmentalization of inflammatory cells in the nasal mucosa and peripheral blood.

Humans↗

PubMed1996

Nonreleasing basophils convert to releasing basophils by culturing with IL-3.

The extent of basophil histamine release initiated by IgE cross-linking stimuli has been known to vary greatly among donors. Studies on anti-IgE nonreleasing basophils are useful in understanding the IgE-specific control mechanism of mediator release. We attempted to determine (1) whether a mutation of Fc epsilon RI is present in nonreleasing basophils and (2) whether treatment with IL-3 converts anti-IgE nonreleasing basophils to releasing basophils. Basophils were purified from normal human blood and donors were divided into releasers (maximal histamine release > 5%) and nonreleasers (< 5%). The mutation of Fc epsilon RI alpha, beta, and gamma was evaluated by reverse transcriptase-polymerase chain reaction, and the DNA sequence was determined from amplified polymerase chain reaction products. Although antibodies against Fc epsilon RI failed to cause histamine release in anti-IgE nonreleasing basophils, no primary structural change of Fc epsilon RI was observed in nonreleaser basophils. After culturing with IL-3 for 7 days, nonreleasing basophils released histamine in response to anti-IgE, and dose-response curves of anti-IgE were equal in both releasers and nonreleasers. The conversion of nonreleasing basophils to releasing basophils was evident after 3 days of culture with IL-3. These findings indicate that nonreleasing basophils have recoverable defect(s) in the signal transduction pathway after IgE cross-linking.

Base Sequence↗

PubMed1996

Recombinant soluble form of the human high-affinity receptor for IgE prevents anaphylactic shock in mice.

The ectodomain of the alpha subunit of the human high-affinity receptor for IgE (Fc epsilon RI) has been engineered as a recombinant soluble protein (sFc epsilon RI alpha) and purified in large quantity from the supernatant of transfected mammalian cells. The sFc epsilon RI alpha was apparently heterogeneous in terms of molecular weight (40 to 60 kd), and this heterogeneity was largely due to N-linked carbohydrates on the molecule. The amino terminal sequence was homogeneous and identical to the sequence predicted from the complementary DNA sequence. The amino acid composition of the sFc epsilon RI alpha was in agreement with the values expected from the cDNA sequence. The sFc epsilon RI alpha formed a complex with IgE, and gel filtration analyses of the complex of the sFc epsilon RI alpha and human IgE supported the idea that the stoichiometry of the IgE binding was 1:1. Passive anaphylactic shock in mice was suppressed when the sFc epsilon RI alpha was intravenously injected after sensitization with anti-trinitrophenyl IgE and challenged with the appropriate antigen. In this model the sFc epsilon RI alpha was effective when administered 48 hours before the antigen challenge, but not 24 hours before the challenge. These results suggest that the sFc epsilon RI alpha facilitated the dissociation of IgE from Fc epsilon RI on mast cells in vivo and suppressed type I allergic reactions.

Amino Acid Sequence↗

PubMed1996

Induction of the high-affinity IgE receptor (Fc epsilon RI) on human mast cells by IL-4.

The high-affinity IgE receptor (Fc epsilon RI) is necessary for the induction of IgE-mediated allergic reactions. Cross-linking of Fc epsilon RI expressed on mast cells causes the release of various inflammatory mediators, which trigger allergic reactions. Recently, mast cells lacking Fc epsilon RI have been observed in vivo and in vitro, suggesting the presence of regulational mechanisms in the induction of Fc epsilon RI. In this report, we demonstrate that IL-4 up-regulates Fc epsilon RI in cultured human mast cells, which are grown from cord blood mononuclear cells in the presence of stem cell factor and IL-6, and usually lack Fc epsilon RI expression. At the protein level, the induction of Fc epsilon RI was observed by flow cytometric analysis and the induced Fc epsilon RI expression was stable for at least 23 days in the presence of IL-4. Consistently, Northern blot analysis demonstrated the increase of alpha chain mRNA of Fc epsilon RI and revealed that the up-regulation of Fc epsilon RI occurred at the transcriptional level. Fc epsilon RI induced by IL-4 was functional and caused histamine and beta-hexosaminidase release from mast cells upon cross-linking. Taken together, these results indicate a new role of IL-4 in allergic reactions, besides the stimulation of IgE production.

Cells, Cultured↗

PubMed1996

Expression, but lack of calcium mobilization by high-affinity IgE Fc epsilon receptor I on human epidermal and dermal Langerhans cells.

In atopic dermatitis (AD) patients, IgE molecules are demonstrated on the surface of Langerhans cells (LC). Fc epsilon RI molecules, which are present on the surface of LC in AD patients as well as normal individuals, are responsible for this binding. In this study, we have investigated phenotypic and functional characteristics of Fc epsilon RI on epidermal and dermal cell populations. Epidermal and dermal cell suspensions were prepared enzymatically with dispase followed by either trypsin or collagenase treatment, respectively. Peripheral blood basophils were negatively selected by excluding other leukocytes with surface marker staining. Consistent with previous reports, both peripheral blood basophils and epidermal LC were positively stained with anti Fc epsilon RI monoclonal antibody. In addition, an Fc epsilon RI positive population was demonstrated among dermal HLA-DR positive cells. These cells express significant amounts of HLA-DR molecules (DRHi) and co-express CD 1 a molecules, which identifies them as LC-like dendritic APC of the dermis. No other Fc epsilon RI positive population was found in the other dermal DRMid or DR- populations, except for a minor DRLo population, presumably mast cells. To analyze whether these Fc epsilon RI molecules are signal transducing for LC, intracellular calcium mobilization after crosslinking of Fc epsilon RI was measured with flow cytometry. Following crosslinking, peripheral blood basophils clearly increased intracellular calcium. On the other hand, neither normal epidermal LC nor dermal DRHiCD1a + cells changed their intracellular calcium level after Fc epsilon RI crosslinking. These data indicate that normal epidermal and dermal LC, but not basophils, are resistant to calcium flux following Fc epsilon RI engagement.

Adult↗

PubMed1996

Sialyl Lewis X analog inhibits eosinophil accumulation and late asthmatic response in a guinea-pig model of asthma.

Preferential eosinophil accumulation is characteristic of airway inflammation in asthma. Although little is known about its mechanism, the effect of a sialyl Lewis X analog on airway eosinophilia was examined in a guinea-pig model of asthma. Guinea-pigs were sensitized by repeated inhalation of ovalbumin. After a single inhalation challenge, the animals showed striking airway eosinophilia and a late asthmatic response. In contrast, when guinea-pigs were pretreated intravenously with sialyl Lewis X analog (LX 0104) 1 h before antigen challenge, both eosinophil infiltration in the tracheal wall and the late asthmatic response were significantly inhibited in a dose-dependent manner. In a further in vitro study, LX 0104 significantly suppressed the adhesion of human and guinea-pig eosinophils to human umbilical vein endothelial cells activated with interleukin-1 beta. These results suggest that LX 0104 plays a critical role in antigen-induced airway eosinophilia and the late asthmatic response.

Animals↗

PubMed1996

Phenotypic and molecular characteristics of nasal mucosal gamma delta T cells in allergic and infectious rhinitis.

T cells expressing the T-cell receptor (TCR) gamma delta home in on various epithelia and may play an important role in local immunity to foreign antigens. The nasal mucosa is a potential site for chronic inflammatory diseases, yet little is known about the characteristics of nasal mucosal gamma delta T cells. Using flow cytometry, immunohistochemistry, and RT-PCR, we elucidated the characteristics of nasal mucosal gamma delta T cells in patients with perennial allergic rhinitis (PAR), chronic infective rhinitis (CIR), and seasonal allergic rhinitis (SAR) and in normal subjects. The gamma delta T cells were significantly increased in the nasal mucosa of patients with PAR (PAR, 24.3 +/- 4.5%; CIR, 12.9+/- 2.7%, p < 0.01), unrelated to those in autologous peripheral blood (PAR, 5.6 +/- 0.8%; CIR, 9.6 +/- 2.8%), and they were preferentially distributed in the epithelial compartment (26.7 +/- 2.3%) rather than in the lamina propria (5.4 +/- 2.5%). Of the expanded population of nasal mucosal gamma delta T cells in patients with PAR, CD4+ and CD4-8- gamma delta T cells were selectively increased (p < 0.01). Although nasal intraepithelial gamma delta T cells from all groups of patients and normal subjects dominantly expressed the V gamma 1/V delta 1 genes, and a bias for V gamma 3 gene expression was noted in those of patients with PAR, a significantly larger fraction of nasal mucosal gamma delta T cells in patients with PAR expressed the V gamma 1/V delta 1 TCR (p, 0.01), whereas those of the peripheral blood expressed the V gamma 2/V delta 2 TCR. More than 60% of V gamma 1/V delta 1 TCR+ cells in patients with PAR, were CD45RO+ ("memory cells"), independent of those in their peripheral blood (p < 0.01). Furthermore, a substantial proportion of nasal mucosal gamma delta T cells in patients with PAR synthesized IL-4 and IL-5 but negligible amounts of IFN-gamma. These observations of an increase in the proportions and activation of distinct subsets of nasal mucosal gamma delta T cells and their Th2-type cytokine profile in patients with PAR, unrelated to those in autologous peripheral blood suggest an important role for the oligoclonally expanded expanded nasal mucosal gamma delta T cells in the pathogenesis of PAR.

Adult↗

PubMed1996

The effect of anti-VLA-4 monoclonal antibody on eosinophil accumulation and leukotriene production in nasal mucosa.

Eosinophil derived leukotrienes and platelet activating factor are known to cause nasal swelling. Toxic proteins induce nasal hyperreactivity to non-specific stimuli including histamine. Recent studies strongly suggest that very late activation antigen-4 (VLA-4) on the eosinophil surface plays a prominent role in the recruitment of eosinophils from blood vessels and eosinophil locomotion in inflammatory tissues. To test this hypothesis, we examined the effect of a monoclonal antibody (mAb) to VLA-4 on eosinophil accumulation in nasal mucosa after antigen challenge in a guinea pig model. Here we have demonstrated that the mAb depressed the eosinophil accumulation in nasal mucosa. In addition, we have shown that this mAb also inhibited eosinophil activation and leukotriene production. Our results raise a possibility that eosinophils might be activated during the journey from bloodstream to inflammatory tissues by the adhesion to endothelial cells and fibronectin. VLA-4 might act as a signalling as well as an adhesion receptor on eosinophils.

Animals↗

PubMed1996

[High affinity receptor for immunoglobulin E (Fc epsilon R I)].

The high-affinity receptor for IgE (Fc epsilon R I) has a tetrameric structure composed of one alpha, one beta and two disulfide-linked gamma subunits (alpha beta gamma 2), of which alpha subunit binds IgE with high affinity and beta, gamma subunits transduce intracellular activation signals. We generated recombinant soluble form of the ectodomain of the human Fc epsilon R I alpha subunit (soluble alpha) and monoclonal antibodies again Fc epsilon R I alpha which inhibit IgE-binding. Soluble alpha works not only as a prophylactic agent for allergy but is also effective for on-going allergic reaction. In addition soluble alpha was elucidated to bind to membranous IgE on B cells and inhibit IgE synthesis. Fab fragments of the monoclonal Abs which inhibit IgE-binding were also very effective as anti-allergic agents and humanization of these Abs are underway.

Humans↗

PubMed1995

Soluble form of the human high-affinity receptor for IgE inhibits recurrent allergic reaction in a novel mouse model of type I allergy.

The recombinant soluble form of the human high-affinity receptor for IgE alpha subunit (sFc epsilon RI alpha) is able to block the binding of IgE to the cell surface Fc epsilon RI and prevent the activation of mast cells and basophils. To evaluate its anti-allergic effects in vivo, we established a novel model for type I allergy by transplanting antigen-specific IgE-secreting hybridomas into syngeneic mice. The hybridomas continuously produced anti-2,4,6-trinitrophenyl IgE in vivo, and ear swelling responses could be elicited upon applying picryl chloride to the ears of these mice, which reached their maximum 1-2 h after the antigen challenge. The second swelling response, in extent comparable to the first response, was induced by the second antigen challenge several days later. When the sFC epsilon RI alpha was intravenously administered before the first challenge and periodically between the first and the second challenges, the ear swelling response to the second challenge, but not to the first challenge, was suppressed almost completely. Immunohistochemical examination revealed that treatment with the sFc epsilon RI alpha blocked the binding of IgE to the cell surface IgE receptors after the first challenge. Thus, our results indicate that the sFc epsilon RI alpha suppresses recurrent allergic reactions by preventing IgE binding to the cell surface Fc epsilon RI.

Animals↗

PubMed1995

High affinity IgE receptor (Fc epsilon RI) expression on eosinophils infiltrating the lesions and mite patch tested sites in atopic dermatitis.

Expression of the high affinity IgE receptor (Fc epsilon RI) on eosinophils has recently been reported. This led us to evaluate Fc epsilon RI expression on eosinophils in atopic dermatitis (AD). Double immunofluorescence stainings with an anti-Fc epsilon RI monoclonal antibody (mAb) and a polyclonal antieosinophil cationic protein (ECP) antibody were performed on lesional biopsy specimens from patients with AD and from patients with bullous pemphigoid (BP) as controls. In AD and BP lesions, 77% and 70% of eosinophils expressed Fc epsilon RI, respectively. However, the intensity of Fc epsilon RI staining in AD was much stronger than in BP, suggesting upregulation of Fc epsilon RI expression on eosinophils in AD. In addition, the eosinophils infiltrating AD lesions were stained strongly with anti-CD23 mAb and anti-IgE antibody. At the sites of mite patch testing in AD, Fc epsilon RI-, CD23- and IgE-positive eosinophils were observed to the same degree as in the lesions, and a considerable number of mite antigen-bearing eosinophils were detected. Fc epsilon RI and CD23 were both upregulated on the skin-infiltrating eosinophils in AD and bound IgE molecules.

Adult↗

PubMed1995

Physical association of Fc receptor gamma chain homodimer with IgA receptor.

The receptor for IgA, Fc alpha R, consists of one IgA-binding alpha chain and a signal-transducing dimeric FcR gamma chain. Immunoprecipitation with an anti-Fc alpha R alpha chain monoclonal antibody from the lysates of U937 cells (human monocytic cell line) revealed an association of 20 kd (unreduced) and 10 kd (reduced) molecules to Fc alpha R alpha chain on sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE). These molecules were confirmed to be FcR gamma chain by immunoblotting probed with anti-FcR gamma chain antibody. A serial immunoprecipitation with both antibodies further ascertained the FcR gamma association with Fc alpha R alpha. The lysates precleared with anti-FcR gamma antibody were subjected to the second immunoprecipitation with an anti-Fc alpha R alpha monoclonal antibody. By this preclearance, FcR gamma disappeared, and the Fc alpha R alpha appeared to be significantly decreased on SDS-PAGE, suggesting that a part of Fc alpha R alpha was co-absorbed with FcR gamma. Therefore, it may be likely that Fc alpha R is expressed in two forms, namely, with or without FcR gamma. We next reconstituted the Fc alpha R alpha-FcR gamma association by introducing both chains into host cells. The expression of Fc alpha R alpha was achieved by introducing Fc alpha R alpha alone, and the cointroduction of FcR gamma did not enhance Fc alpha R alpha expression on the cell surface, suggesting again the occurrence of the two forms of FC alpha R.

Amino Acid Sequence↗

PubMed1995

Expression and function of fibronectin binding integrins on rat mast cells.

Adhesion molecules of the integrin family are implicated not only in leukocyte migration but also in leukocyte activation. Here we characterize the expression and function of fibronectin receptor integrins on rat mast cells. A rat basophilic leukemia cell line (RBL-2H3) and phorbol ester-stimulated rat peritoneal mast cells adhered to fibronectin (FN), vitronectin and fibrinogen. These mast cells expressed fibronectin receptor integrins, including very late antigen (VLA)-4, VLA-5 and vitronectin receptor (VNR), as estimated by immunofluorescent staining and inhibition of FN adherence by newly established mAbs reactive with the rat alpha 4 (MR alpha 4-1), alpha 5 (HM alpha 5-1) or beta 3 (HM beta 3-1) chains of the integrin molecules. The beta-hexosaminidase release, a marker for mast cell degranulation, triggered by high affinity IgE receptor (Fc epsilon RI)-mediated stimulation, was enhanced by adhesion of RBL-2H3 cells to either immobilized FN, MR alpha 4-1, HM alpha 5-1 or HM beta 3-1. This FN enhancement of beta-hexosaminidase release was inhibited by soluble MR alpha 4-1, HM alpha 5-1 and HM beta 3-1 as well as by GRGDSP and DELPQLVTLPHPNHLGPEILDVPST peptides which abrogate VLA-5/VNR and VLA-4 binding to FN respectively. In vivo, passive cutaneous anaphylaxis induced by IgE anti-DNP and DNP-BSA was inhibited by concurrent s.c. injection of MR alpha 4-1, HM alpha 5-1 and HM beta 3-1. These results demonstrate that FN receptor integrins expressed on rat mast cells play an important role in regulating mast cell activation both in vitro and in vivo.

Amino Acid Sequence↗

PubMed1995

Differential responsiveness of Langerhans cell subsets of varying phenotypic states in normal human epidermis.

Epidermal Langerhans cell heterogeneity is poorly understood with regard to phenotypic characteristics, such as the expression of human leukocyte antigen (HLA)-DR, integrin, and Fc receptor molecules, as well as functional characteristics, such as the ability to process and present antigens or produce cytokines during various phases of immigration and maturation. Technical limitations of Langerhans cell number have limited functional assays on putative Langerhans cell subsets in in vivo epidermis. Therefore, we used flow cytometry for simultaneous phenotypic and functional assessment at the single-cell level within the Langerhans cell population. Freshly isolated human epidermal cell suspensions were stained with a battery of monoclonal antibodies, including anti-HLA-DR, -CD1a, -CD1c, -CD11c, -Fc gamma RII, and -Fc epsilon RI. Two distinct Langerhans cell subsets were identified by their different levels of HLA-DR expression. The DRHi subset expressed higher amounts of CD11c and exhibited greater cytoplasmic complexity and higher baseline calcium than the DRLo subset (p < or = 0.03 for each). Some subjects also expressed high levels of Fc epsilon RI in the DRHi, CD11cHi subset. To determine whether these phenotypic subsets may exhibit differential signal-transduction functional properties, Langerhans cells were partially enriched over Ficoll-Hypaque and their cytosolic mobilization after the addition of ionomycin was analyzed using the calcium indicator, indo-1, in conjunction with quantitative analysis of HLA-DR expression. By this real-time flow cytometric analysis, a new subpopulation was revealed within the DRLo Langerhans cell subset. This subset increased its cytosolic calcium concentration much more than the other two subsets (change in indo-1 blue:violet emission ratio of 37.33 +/- 2.34 in the Hi Flux DRLo subset versus 13.23 +/- 0.29 in the Lo Flux DRLo subset, and versus 7.6 +/- 2.99 in the Lo Flux DRHi subset). These data indicate that functional, as well as phenotypic, subsets of Langerhans cells exist within normal human epidermis. Their responses to physiologic stimuli may relate to maturational stage or the level of in vivo activation.

Adult↗

PubMed1995

Do structural changes of T cell receptor complex occur in tumor-bearing state?

T cells in tumor-bearing mice and cancer patients were recently shown to be devoid of CD3-zeta chain, a signal-transducing invariant chain in T cell receptor (TCR) complex, and p56lck tyrosine kinase. In the present study, we investigated the structure and function of TCR complex in T cells from BALB/c mice bearing CSA1M fibrosarcoma. The expressions of TCR chains and p56lck in a T cell-enriched population from spleen were analyzed. Almost complete loss of CD3-zeta and p56lck was observed in the preparation from tumor-bearing mice as assessed by immunoblotting analysis using whole cell lysates, whereas the amounts of other TCR chains were relatively unchanged. However, these changes were due to the increase of contaminating Mac-1+ cells in the spleen of tumor-bearing mice because: 1) the removal of Mac-1+ cells led to the restoration of CD3-zeta and p56lck; and 2) CD3-zeta was clearly present when the preparation was solubilized with ionic detergent. Fc receptor gamma chain detected in the preparation from tumor-bearing mice disappeared along with the removal of Mac-1+ cells. These observations were further supported by the finding that addition of Mac-1+ cells from tumor-bearing mice to normal T cells resulted in loss of CD3-zeta, leaving CD3-epsilon largely intact. When T cells from tumor-bearing mice were highly purified by depletion of Mac-1+ cells, these T cells contained normal amounts of CD3-zeta at mRNA, protein, and surface levels, and expressed the properly assembled TCR complex on their cell surface. Moreover, stimulation of the TCR in these T cells by anti-TCR antibodies resulted in a comparable Ca2+ mobilization to that observed in normal T cells. These results suggest that no structural changes occur in TCR complex in our tumor-bearing mice, and that complete depletion of Mac-1+ cells in important to assess the structure of TCR complex.

Animals↗

PubMed1995

High affinity IgE receptor-mediated prostaglandin E2 production by monocytes in atopic dermatitis.

High affinity IgE receptor (Fc epsilon R I) expression on monocytes and its upregulation on monocytes from patients with atopic dermatitis (AD) have been recently reported. In this study, we investigated whether prostaglandin E2 (PGE2) release from AD monocytes was Fc epsilon R I-dependent or not. The monocytes were stimulated with anti-Fc epsilon R I monoclonal antibody (mAb) and anti-Fc epsilon R II mAb. Cross-linking of Fc epsilon R I, but not that of Fc epsilon R II induced PGE2 release from monocytes. In order to confirm that the PGE2 release is IgE-dependent, stimulation with IgE+anti-IgE, IgG+anti-IgG and immune complexes made by incubation with AD patients' serum and recombinant Der fII (rDer fII-IC) were carried out in the culture. Significant PGE2 release by all the stimulants was observed, as compared with spontaneous release. PGE2 release by immune complex made by incubation with IgE-absorbed AD serum and rDer fII was much lower than that by rDer fII-IC. In monocytes from nonatopic donors, significant PGE2 release was observed when stimulated with IgE+anti-IgE, IgG+anti-IgG, rDer fII-IC, but not with anti-FC epsilon R I mAb and anti-Fc epsilon R II mAb. However, the release were significantly lower than respective PGE2 releases from AD monocytes. Taken together, cross-linking of Fc epsilon R I and IgE induced a PGE2 release from monocytes. This is a first report demonstrating an Fc epsilon R I-dependent mediator release from monocytes of AD patients.

Antigen-Antibody Complex↗

PubMed1995

Lymphocyte subsets of the nasal mucosa in perennial allergic rhinitis.

T cells have been considered to play a primary role in IgE-mediated atopic diseases, yet little is known about the T-cell subsets in the nasal mucosa of patients with perennial allergic rhinitis. To elucidate the characteristics of T cells at the site of allergic inflammation, we analyzed the proportions, phenotypes, stages of differentiation, and distribution of T-cell subsets in the nasal mucosa of 15 patients with house-dust-mite perennial allergic rhinitis (PAR) and 14 patients with chronic infective rhinitis (CIR), using flow cytometry and immunohistochemistry. We also examined the T-cell subsets in the peripheral blood (PBL) in conjunction with those of the nasal mucosa in 10 patients with PAR and in nine patients with CIR. Our results revealed no obvious difference in the percentage of nasal CD3+ T cells, CD8+ T cells, and alpha beta T cells in the PAR and CIR patients. In contrast, CD4+ T cells (p < 0.05), CD3+4-8- double-negative T cells, (p < 0.01), and gamma delta T cells (p < 0.01) were significantly increased in the nasal mucosa of PAR patients. A majority of the CD4+ T cells in the nasal mucosa of PAR patients coexpressed the CD45RO surface molecule, and a predominant proportion of CD4+ T cells in the nasal coexpressed the CD45RO surface molecule, and a predominant proportion of CD4+ T cells in the nasal epithelium were CD45RO+. The ratio of CD4+ CD45RO+:CD4+ CD45RA+ T cells in the allergic patients' nasal mucosa was significantly greater than that in autologous peripheral blood (p < 0.01). The proportion and stages of activation and differentiation of T-cell subsets in the allergic patients' nasal mucosa were independent of those in the peripheral blood. An increase in the proportion of natural killer (NK) cells was observed in the nasal mucosa of CIR patients. Taken together, our results suggest that nasal T cells exhibit distinct patterns of distribution, differentiation, and activation in different inflammatory conditions of the nose. PAR is characterized by a selective increase in CD4+ memory T cells, CD3+4-8- double-negative T cells, B cells, and gamma delta T cells in the nasal mucosa. The increase in CD4+ memory T cells in the allergic nasal epithelium may have critical implications in the pathogenesis of PAR.

Adult↗