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C Ra

Publications and source records attributed to C Ra.

At least 73 records · Page 4Linked to original sources
PubMed1999

Age-dependent increase of IgE-binding and FcepsilonRI expression on circulating basophils in children.

Peripheral blood basophils are sparse in the circulation, but they express high-affinity receptors for IgE (FCepsilonRI) and bind IgE efficiently. The present study was performed to elucidate the role of IgE bound on the basophil surface in the development of allergic responses during infancy and early childhood. IgE-binding and FcepsilonRI expression on basophils were evaluated by two-color flow cytometry. Basophil-bound IgE increased rapidly and reached adult levels during infancy in atopic patients, while it gradually increased with advancing age in parallel with serum IgE in normal controls. IgE-binding and FcepsilonRI expression in atopic children were higher than in normal controls among various age groups. They correlated with serum IgE levels but reached a plateau when serum IgE exceeded 300 ng/mL. A low, but significant level of FcepsilonRI expression was observed on cord blood basophils, although IgE-binding was usually undetectable. Incubation of cord blood with IgE rapidly saturated the preexisting IgE receptors and basophil-bound IgE levels increased. When neonatal basophils were cultured for 48 h with IgE, FcepsilonRI expression was upregulated dose-dependently and IgE-binding increased further. The up-regulation of FcepsilonRI was completely inhibited by cycloheximide, indicating that it was dependent on de novo protein synthesis. These results suggest that IgE-binding on basophils serves as a sensitive indicator of allergic sensitization, and that IgE functions as a positive regulator of FcepsilonRI expression in vivo.

Adolescent↗
PubMed1999

Role of mast cells as a trigger of inflammation in Helicobacter pylori infection.

Helicobacter pylori (H. pylori) induces severe inflammation and plays a key role in gastric mucosal diseases. In general, mast cells have been believed to play an important role in inflammation. Although mast cells were detected in the gastric mucosa, the role of mast cells in the gastric mucosal inflammation caused by H. pylori is still unclear. Therefore, we examined the effects of H. pylori water extract on the degranulation of mast cells to clarify the role of these cells in gastric mucosal inflammation induced by H. pylori. Mast cells prepared from rat abdominal cavity were incubated with H. pylori for 30 min. The protein concentrations of H. pylori water extract used in this study were 0.5-3 mg/ml. The degranulation of mast cells were monitored morphologically by phase contrast microscopy equipped with time-lapse video recording system and biochemically by measuring histamine and beta-hexosaminidase. H. pylori water extract induced the degranulation of mast cells dose-dependently. The identical experiment was performed without extracellular calcium, and no significant degranulation was found. The data indicates that the degranulation of mast cells by H. pylori water extract depend on extracellular calcium. The present results indicate that H. pylori might be involved in the gastric mucosal inflammation as a trigger of mast cell degranulation for releasing chemical mediators.

Albinism↗
PubMed1998

Resistance of Fc receptor- deficient mice to fatal glomerulonephritis.

Immune complex-mediated inflammation is a common mechanism of various autoimmune diseases. Glomerulonephritis (GN) is one of these diseases, and the main mechanism of the induction of GN has been unclear. We examined the contribution of Fc receptors in the induction of nephrotoxic GN by establishing and analyzing mice deficient in the Fc receptor gamma chain (FcRgamma). Whereas all wild-type mice died from severe glomerulonephritis with hypernitremia by administration of anti-glomerular basement membrane (GBM) antibodies, all FcRgamma-deficient mice survived. Histologically, wild-type mice showed glomerular hypercellularity and thrombotic changes, whereas the renal tissue in FcRgamma-deficient mice was almost intact. Deposition of anti-GBM antibody as well as complement components in the GBM were equally observed in both wild-type and knockout mice. These results demonstrate that the triggering of this type of glomerulonephritis is completely dependent on FcR+ cells.

Animals↗
PubMed1998

Human mast cells produce IL-13 by high-affinity IgE receptor cross-linking: enhanced IL-13 production by IL-4-primed human mast cells.

BACKGROUND: Mast cells play a central role not only in the early phase of the allergic reaction, but also participate in the late phase of the allergic reaction through the allergen and IgE-dependent release of multifunctional cytokines. OBJECTIVE: Using the recently established culture system for human mast cells, we examined the expression of a variety of cytokines in cord blood-derived human cultured mast cells (HCMCs) in response to different stimuli. METHODS: HCMCs were grown from cord blood mononuclear cells in the presence of stem cell factor and IL-6 for 10 weeks. Cytokine mRNA expression in HCMCs by the different stimuli was examined by RT-PCR. Then taking 2 important cytokines, IL-13 and IL4, that share several functional properties and play important roles in allergic diseases, we examined protein as well as mRNA expression of both cytokines in HCMCs. RESULTS: HCMCs did not express either IL-13 or IL-4 spontaneously. Stimulation with PMA + A23187 induced the expression of IL4 protein, as well as IL-13 protein, in their cytoplasm, although IL-4 secreted in the supernatant was below detectable levels in contrast to a significant amount of IL-13. Stimulation of HCMCs by cross-linking of the high-affinity IgE receptor (Fc(epsilon)RI) induced the expression of IL-13 mRNA and protein, but not IL4. Although we previously found that IL-4 upregulates Fc(epsilon)RI expression on HCMCs, when HCMCs were first cultured in the presence of IL4 and then activated through FC(epsilon)RI cross-linking, remarkable increase was found in IL-13 production. Furthermore, although IL-4 was still undetectable at protein level, IL-4 mRNA expression was induced in the IL-4-primed HCMCs stimulating Fc(epsilon)RI cross-linking. In addition, we examined the effects of these cytokines on the surface molecule expression in HCMCs. Although IL4 remarkably upregulated lymphocyte function-associated antigen-1, intercellular adhesion molecule-1, and Fc(epsilon)RI expression and downregulated c-kit expression in HCMCs, IL-13 did not. CONCLUSIONS: Our observation that HCMCs produce IL-13 on cross-linking of Fc(epsilon)RI, which was enhanced by IL-4 priming, supports an important role of mast cells in amplification of allergic reaction and further suggests one of the mechanisms enhancing mast cell function in the microenvironment.

Antibodies, Anti-Idiotypic↗
PubMed1998

The Fc receptor (FcR) gamma subunit is essential for IgE-binding activity of cell-surface expressed chimeric receptor molecules constructed from human high-affinity IgE receptor (Fc epsilon RI) alpha and FcR gamma subunits.

The Fc receptor (FcR) gamma subunit was originally discovered as a homodimeric subunit of the high-affinity IgE receptor (FcepsilonRI). But it was recently found to be a common signal-generating subunit of Fc receptors including IgG Fc receptors (FcgammaRs) and IgA Fc receptor (FcalphaR), and furthermore to generate a signal also with stimuli through non-immune receptors. In addition, it plays an essential role in cell-surface expression of the FcepsilonRI and the FcgammaRIIIA isoform and also regulates cell-surface expression and ligand-binding affinity of the FcgammaRI. In this report, we addressed the possibility that the FcRgamma could affect the correct folding of the IgE-binding region of the FcepsilonRIalpha subunit by using the chimeric receptor molecules constructed from human FcepsilonRIalpha and FcRgamma. Furthermore, we demonstrated that the seven amino acid residues in the C-terminal region on the extracellular domain of the FcepsilonRlalpha were essential for maintaining the IgE-binding activity of the FcepsilonRIalpha exodomain on the cell membrane and/or may affect the correct folding of the alpha subunit itself within the cell.

Animals↗
PubMed1998

Production of IL-13 by human lung mast cells in response to Fcepsilon receptor cross-linkage.

BACKGROUND: Cross-linkage of the high affinity Fcepsilon receptors (FcepsilonRI) on the surface of the mast cell by the allergen-IgE complex is a central event in the induction of allergic inflammatory reactions. However, the precise roles of human mast cells in the perpetuation of allergic inflammation is not well known. IL-13 plays an important role in the regulation of allergic inflammation, especially being involved in the induction of IgE synthesis. OBJECTIVE: We investigated whether human lung mast cells have the capacity to produce IL-13 by cross-linking of the FcepsilonRI. METHODS: Lung mast cells were purified by affinity magnetic selection with monoclonal antibody YB5.B8 against c-kit to achieve a final mast cell purity of more than 93%. Purified mast cells were precultured with human myeloma IgE (3 microg/mL) for 16 h before challenge with stem cell factor (SCF) (50 ng/mL) and anti-IgE (1 microg/mL). By RT-PCR, ELISA and immunocytochemistry, we evaluated the capacity of human lung mast cells to express and produce IL-13. RESULTS: IgE-dependent activation of human lung mast cells caused an increase in IL-13 mRNA expression which persisted for up to 12 h. Immunoreactive IL-13 was detectable 24 h after activation of sensitized lung mast cells with SCF and anti-IgE in 6 of 13 non-asthmatic donors and a million of mast cells secreted 106.7 +/- 42.65 (mean +/- SE) pg of IL-13 into the culture supernatants. SCF alone induced 61.63 +/- 31.12 pg of IL-13 from 106 mast cells. This difference was statistically significant (P = 0.028, n = 13). Furthermore, we confirmed by immunocytochemistry that immunological activation induced an increase of intracellular IL-13. CONCLUSION: These findings demonstrate the capacity of human lung mast cells to transcribe IL-13 after IgE-dependent activation and to synthesize and release IL-13.

Cells, Cultured↗
PubMed1998

Cultured basophils but not cultured mast cells induce human IgE synthesis in B cells after immunologic stimulation.

By generating human mast cells and basophils from umbilical cord blood mononuclear cells cultured in the presence of appropriate cytokines, we investigated whether these two cultured cells could provide the cytokine and cell contact signals that are required to induce IgE synthesis in B cells. To activate cultured mast cells and basophils, cross-linking of cell surface high-affinity IgE receptor (Fc epsilonRI) was performed with specific antigen after sensitization with murine IgE. Upon Fc epsilonRI stimulation, basophils, but not mast cells, secreted significant amounts of immunoreactive IL-4 and IL-13 and expressed detectable CD40 ligand (CD40L) and a very low level of Fas ligand (FasL). These observations at the protein level were consistent with the data obtained at the gene transcriptional level, except for the faint expression of only IL-13 mRNA in mast cells. When added to normal human B cells, activated basophils induced IgE and IgG4 synthesis as well as soluble CD23 release. In contrast, neither IgE nor IgG4 synthesis could be induced by the interaction of B cells with activated mast cells, even in the presence of recombinant IL-4. The induction of IgE synthesis by activated basophils was completely abrogated by two neutralizing MoAbs against IL-4 and IL-13 and by a soluble form of CD40. This abrogation was accompanied by abolished mature C epsilon transcription in both cases. Addition of anti-FasL MoAb, however, did not significantly affect IgE induction mediated by activated basophils. These results demonstrate that unlike cultured mast cells, cultured basophils produce biologically active IL-4 and IL-13 and express functional CD40L after Fc epsilonRI stimulation, thereby contributing to IgE production by B cells, and suggest that relatively weak expression of FasL by cultured basophils is not involved in IgE regulation.

B-Lymphocytes↗
PubMed1998

Distinct contribution of Fc receptors and angiotensin II-dependent pathways in anti-GBM glomerulonephritis.

BACKGROUND: The contribution of antibody and/or immune-complex to the pathogenesis of immunologically-mediated glomerulonephritis is not fully understood, although it has been recently clarified that Fc receptors (FcRs) play critical roles in the inflammatory cascade. We therefore re-evaluated the classical model of glomerulonephritis, anti-glomerular basement membrane antibody-induced glomerulonephritis (Anti-GBM GN), from the standpoint of FcRs and also investigated the residual FcR-independent mechanisms. METHODS: We adopted an Anti-GBM GN mouse model that has two strains deficient in the FcR gamma chain [gamma(-/-)] or Fc gammaRIIB [RII(-/-)], and analyzed functional (urinary protein, serum creatinine, BUN) and pathological changes of the glomeruli. For the analyses of FcR-independent mechanisms, several doses of nephrotoxic serum were applied, and then mice were treated either with cobra venom factor or an angiotensin II type 1 receptor antagonist in gamma(-/-) mice. RESULTS: In gamma(-/-) mice, renal injuries were dramatically attenuated with an absence of polymorphonuclear cell (PMN) influx, while RII(-/-) mice suffered accelerated glomerular injuries in spite of a normal PMN influx. In the absence of FcR-dependent effects in gamma(-/-) mice, the FcR-independent pathway lead to chronic renal damage characterized by mesangial proliferation and progressive expansion of mesangial area, with monocyte/macrophage accumulation and with the expression of alpha smooth muscle actin in the mesangial cells and interstitium. Those injuries in gamma(-/-) mice were not attenuated by the decomplementation, but completely abolished by using an angiotensin II type 1 receptor antagonist. CONCLUSIONS: Our results clearly demonstrate that FcRs play a pivotal role in Anti-GBM GN, especially in its acute phase. We further clarified the existence of FcR and complement-independent but antibody-dependent pathway. Furthermore, we found that those pathological changes were strongly related to the renin-angiotensin system.

Actins↗
PubMed1998

Chronic oral antigen exposure induces lymphocyte migration in anaphylactic mouse intestine.

Persistent diarrhea, vomiting, and dehydration are symptoms often seen in patients suffering from food allergy after chronic antigen exposure; however, the precise mechanisms involved have not been well defined. In an effort to clarify the mechanisms of the chronic intestinal changes attributable to genuine IgE-mediated anaphylactic reactions induced by orally administered antigen, a mouse model was established by s.c. implantation of a murine hybridoma capable of producing monoclonal anti-trinitrophenyl IgE antibody, and the morphologic and immunologic changes occurring in the intestine upon chronic antigen exposure were investigated. In the early stage after ingestion of the antigen, diarrhea and noticeable infiltration of mast cells as well as eosinophils into the lamina propria were observed. A substantial increase in serum histamine levels as well as an increase in leukotriene C4 synthesis in the jejunal mucosa were observed 1 h after antigen challenge. Also, the synthesis of leukotriene B4 was significantly elevated for up to 9 h after antigen challenge. The expression of both intercellular adhesion molecule-1 (ICAM-1) on mucosal vascular endothelial cells and IAd on epithelial cells was markedly enhanced, and noticeable infiltration of eosinophils and lymphocytes was also confirmed in the mouse model after chronic antigen exposure. These findings suggest that oral antigen exposure induces anaphylactic reactions in the intestine mediated by mast cells and eosinophils in response to the IgE-antigen complex in the early phase, and also induces lymphocyte migration after chronic antigen exposure.

Administration, Oral↗
PubMed1998

IgE-Fc epsilonRI-mast cell axis in the allergic cycle.

The IgE and allergen dependent activation of mast cells via the high affinity IgE receptor (Fc epsilonRI) resulting in the release of inflammatory mediators is critical to the pathogenesis of atopic diseases like bronchial asthma and allergic rhinitis. However, mast cells are also involved in certain IgE-independent biological responses, and recent studies have highlighted the role of mast cells in host defense. In the light of this background, we have discussed our recent data on the immunophenotypic characteristics of nasal mast cells in patients with perennial allergic rhinitis (PAR) and chronic infective rhinitis (CIR) based on the expression of cytokines, the Fc epsilonRI, the cell-bound IgE, as well as the IgE-mediated mediator release (before and after saturation of the IgE receptors). Although nasal mast cells (NMC) from both groups of patients expressed a variety of cytokines, significant differences were observed in the proportion of cytokine expressing cells between PAR and CIR. NMC from PAR patients exhibited increased Fc epsilonRI expression, cell-bound IgE and IgE-mediated mediator release as compared with NMC from CIR patients, even after saturation of the IgE receptors. The density of IgE receptors and IgE molecules in NMC of PAR patients correlated well with the levels of serum IgE, and IL-4 upregulated the expression of the Fc epsilonRI in NMC. Moreover, NMC from PAR patients induced IgE synthesis in B cells. Taken together, these results and the recently demonstrated IgE-induced upregulation of the Fc epsilonRI expression in mast cells suggest critical roles for mast cells in promoting the allergic reaction through an IgE-Fc epsilonRI-mast cell axis.

Chronic Disease↗
PubMed1997

Association with FcRgamma is essential for activation signal through NKR-P1 (CD161) in natural killer (NK) cells and NK1.1+ T cells.

Natural killer (NK) cells exhibit cytotoxicity against variety of tumor cells and virus-infected cells without prior sensitization and represent unique lymphocytes involved in primary host defense. NKR-P1 is thought to be one of NK receptors mediating activation signals because cross-linking of NKR-P1 activates NK cells to exhibit cytotoxicity and IFN-gamma production. However, molecular mechanism of NK cell activation via NKR-P1 is not well elucidated. In this study, we analyzed the cell surface complex associated with NKR-P1 on NK cells and found that NKR-P1 associates with the FcRgamma chain which is an essential component of Fc receptors for IgG and IgE. The association between FcRgamma and NKR-P1 is independent of Fc receptor complexes. Furthermore, NK cells from FcRgamma-deficient mice did not show cytotoxicity or IFN-gamma production upon NKR-P1 cross-linking. Similarly, NK1.1+ T cells from FcRgamma-deficient mice did not produce IFN-gamma upon NKR-P1 crosslinking. These findings demonstrate that the FcRgamma chain plays an important role in activation of NK cells via the NKR-P1 molecule.

Animals↗
PubMed1997

Roles of C-terminal Src kinase in the initiation and the termination of the high affinity IgE receptor-mediated signaling.

As an attempt to analyze the roles of C-terminal Src kinase (Csk) in the high affinity IgE receptor (FcepsilonRI)-mediated signaling, we overexpressed Csk, a membrane-targeted form of Csk (mCsk), and a kinase-defective, membrane-targeted form of Csk (mCsk(-)) in rat basophil leukemia (RBL) 2H3 cells. Specific activity of Lyn at the basal state was decreased in Csk-expressing cells, and further decreased in mCsk-expressing cells. In mCsk(-)-expressing cells, basal specific activity of Lyn was increased, thereby indicating that mCsk(-) functioned as a dominant negative molecule. The onset of FcepsilonRI-mediated Lyn activation was delayed in Csk-expressing cells, and further delayed in mCsk-expressing cells. In mCsk(-)-expressing cells, Lyn activation was rapid and quite long lasting. These findings indicate (i) Csk negatively regulates rapid FcepsilonRI/Lyn coupling, and (ii) Csk activity is potentially required for its termination. The onsets of the series of events including tyrosyl phosphorylation of Syk, mitogen-activated protein (MAP) kinase activation, elevation of intracellular calcium concentration ([Ca2+]i), and histamine release were all stepwisely delayed in Csk-expressing cells and in mCsk-expressing cells. The durations of Syk phosphorylation and MAP kinase activation also closely correlated with those of Lyn activation, but [Ca2+]i elevation and histamine release followed different temporal patterns: the delayed responses in Csk-expressing cells and in mCsk-expressing cells led to sustained [Ca2+]i oscillation and histamine release, while the prompt responses in parent cells and mCsk(-)-expressing cells rapidly subsided. These findings provide further evidence that the initiations of the FcepsilonRI-mediated signals are upstreamly regulated by Src family protein tyrosine kinases and revealed that their terminations are regulated by Lyn-dependent (Syk and MAP kinase) and -independent ([Ca2+]i elevation and histamine release) mechanisms.

Amino Acid Sequence↗
PubMed1997

Interleukin-4 induces homotypic aggregation of human mast cells by promoting LFA-1/ICAM-1 adhesion molecules.

We report here that interleukin-4 (IL-4) induces homotypic aggregation of cultured human mast cells, grown from cord blood mononuclear cells in the presence of stem cell factor and IL-6. This aggregation was specifically induced by IL-4, because other cytokines including IL-1alpha, IL-1beta, IL-2, IL-3, IL-5, IL-9, IL-10, interferon-gamma, IL-12, granulocyte-macrophage colony-stimulating factor, NGF-beta, and tumor necrosis factor-alpha failed to show such effect. Flow cytometric analysis of the cultured mast cells showed that IL-4 increases the expression of lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1), but not of very late antigen (VLA) family adhesion molecules or vascular cell adhesion molecule-1 (VCAM-1). Neutralizing monoclonal antibodies specific for LFA-1alpha, LFA-1beta, or ICAM-1 inhibited the IL-4-induced homotypic aggregation of the mast cells, indicating that the aggregation was mediated mainly by LFA-1/ICAM-1 interaction. In addition, IL-4-treated but not untreated mast cells bound to immobilized ICAM-1. This binding was also inhibited by anti-LFA-1 or anti-ICAM-1. These results show that IL-4 promotes expression of ICAM-1 and LFA-1 molecules on mast cells, and suggest that IL-4 may contribute to the migration of mast cells into the inflamed tissue and to the cellular interaction with other inflammatory cells by upregulating adhesion molecules.

Antibodies, Monoclonal↗
PubMed1997

Nasal mast cells in perennial allergic rhinitics exhibit increased expression of the Fc epsilonRI, CD40L, IL-4, and IL-13, and can induce IgE synthesis in B cells.

Cross-linking of allergen specific IgE bound to the high affinity IgE receptor (FC epsilonRI) on the surface of mast cells with multivalent allergens results in the release of both pre-formed and newly generated mediators, and in the manifestation of allergic symptoms. The expression of Fc epsilonRI, and the synthesis of IgE are therefore critical for the development of allergic diseases. In this study, we report that nasal mast cells (NMC) from patients with perennial allergic rhinitis (PAR) expressed significantly greater levels of the Fc epsilonRI, CD40L, IL-4, and IL-13 as compared to NMC from patients with chronic infective rhinitis (CIR). The level of Fc epsilonRI expression in NMC of PAR patients strongly correlated with the levels of serum total (r = 0.8, P < 0.003) and specific IgE (r = 0.89, P < 0.0004) antibodies. In addition, stimulation of NMC with IL-4, upregulated the Fc epsilonRIalpha chain expression both at the protein and mRNA levels, as detected by flow cytometry and reverse transcriptase-polymerase chain reaction. Furthermore, NMC from PAR, but not CIR, patients induced IgE synthesis by purified B cells in the presence of Der fII (mite antigen). These results suggest novel and critical roles for mast cells in promoting the allergic reaction through the increased expression of Fc epsilonRI and by enhancing and amplifying the IgE production, within the local microenvironment.

Adult↗
PubMed1997

Lack of cognate help by CD4+ T cells and anergy of CD8+ T cells are the principal mechanisms for anti-leukocyte function-associated antigen-1/intercellular adhesion molecule-1-induced cardiac allograft tolerance.

Combined treatment with anti-leukocyte function-associated antigen-1 (LFA-1) and anti-intercellular adhesion molecule-1 (ICAM-1) monoclonal antibodies leads to allograft tolerance in murine cardiac transplantation. In the present study, we analyzed the mechanisms for this tolerance induction. In the tolerant mice, proliferative response of splenic T cells against donor-type cardiac myocytes and of CD8+ T cells against donor-type alloantigens was impaired as compared with responses in naive or rejected mice, but was completely restored with exogenous interleukin 2. This suggests that class I-restricted CD8+ T cells of tolerant mice were rendered anergic against donor-type alloantigens in the periphery. In contrast, proliferative response of CD4+ T cells against donor-type alloantigens in vitro was comparable between tolerant and naive mice. When heart and skin grafts from the same donor (BALB/c [H2d]) were simultaneously transplanted to C3H mice (H2k), both were rejected within 29 days, even though the mice were similarly treated with anti-LFA-1 and anti-ICAM-1 monoclonal antibodies. In contrast, when heart graft from BALB/c and skin graft from third-party donor (C57BL/6 [H2b]) were simultaneously transplanted to C3H mice under the same condition, the heart graft was accepted indefinitely and the skin graft was rejected. These findings suggest that the peripheral tolerance against cardiac allografts could be induced by selective inactivation of alloreactive CD8+ T cells resulting from the lack of cognate help by CD4+ T cells.

Animals↗
PubMed1997

Development of atopic dermatitis-like skin lesion with IgE hyperproduction in NC/Nga mice.

Atopic dermatitis (AD) usually develops in patients with an individual or family history of allergic diseases, and is characterized by chronic relapsing inflammation seen especially in childhood, association with IgE hyperproduction and precipitation by environmental factors. However, the exact etiology of AD has been unclear. To further explore the pathogenesis and treatment of AD, a suitable animal model is required. We found that skin lesions, which were clinically and histologically very similar to human AD, spontaneously appeared on the face, neck, ears and dorsal skin of inbred NC/Nga mice when they were raised in non-sterile (conventional) circumstances, but not under specific pathogen-free conditions. Plasma levels of total IgE in conventional NC/Nga mice were markedly elevated from 8 weeks of age, correlating with clinical skin severity of dermatitis. Immunohistochemical examination of the skin lesion showed increased numbers of mast cells and CD4+ T cells containing IL-4 necessary for IgE synthesis. Thus, NC/Nga mice suffered from dermatitis very similar to human AD with IgE hyperproduction, which may be triggered by some environmental factor(s).

Animals↗
PubMed1997

A monoclonal antibody against very late activation antigen-4 inhibits eosinophil accumulation and late asthmatic response in a guinea pig model of asthma.

Preferential eosinophil accumulation is a characteristic of airway inflammation in asthma. Although little is known about its mechanism, recent in vitro observations suggest that the very late activation antigen-4 (VLA-4, CD49d/CD29) and vascular cell adhesion molecule-1 (VCAM-1) adhesion pathway may be involved in specific eosinophil migration. To test this hypothesis, we studied the effect of an anti-VLA-4 monoclonal antibody (mAb) on the airway eosinophilia in a guinea pig model of asthma. Guinea pigs were sensitized by repeated inhalation of ovalbumin. After a single inhalation challenge, the animals showed a striking airway eosinophilia and late asthmatic response (LAR). In contrast, when guinea pigs were pretreated intravenously at 2 h before antigen challenge with a rat antimouse VLA-4 mAb, PS2/3, cross-reacting with guinea pig eosinophils and lymphocytes, eosinophil, basophil and lymphocyte infiltration in the tracheal wall was significantly inhibited as well as LAR in a dose-dependent manner. These results suggest that VLA-4 plays a critical role in antigen-induced airway eosinophilia and LAR.

Animals↗