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Alpha Chain (alpha + chain)

Distribution by Scientific Domains

Medical Sciences	60%

Selected Abstracts

Low expression of the interleukin (IL)-4 receptor alpha chain and reduced signalling via the IL-4 receptor complex in human neonatal B cells

IMMUNOLOGY, Issue 1 2006
Cuixia Tian
Summary Diminished neonatal antibody responses following infection or immunization may stem in part from intrinsic characteristics of neonatal B cells. In this study, we used B-cell subset sorting combined with gene expression assays to investigate major differences in the expression of host genes in neonatal and adult naïve B cells. We discovered significantly reduced expression of the interleukin (IL)-4 receptor alpha chain and reduced IL-4-induced signalling in neonatal B cells. Neonatal naïve B cells were susceptible to more rapid and more profound levels of apoptosis when cultured in vitro. They also exhibited a limited response to IL-4 treatment compared with adult cells. The expression level of the IL-13 receptor alpha 1 chain, a key component of the IL-13 receptor/IL-4 type II receptor, and the response to IL-13 treatment for protection against apoptosis in neonatal B cells were similar to those of the adult B cells. These studies suggest a possible mechanism underlying the limited magnitude and durability of neonatal antibody responses. [source]

The MUC1 oncoprotein as a functional target: Immunotoxin binding to ,/, junction mediates cell killing

INTERNATIONAL JOURNAL OF CANCER, Issue 1 2009
Daniel B. Rubinstein
Abstract MUC1, a heavily glycosylated mucin, has generated considerable interest as a target for tumor killing because of its overexpression in malignancies. Full-length MUC1 (MUC1/TM) is proteolytically cleaved after synthesis generating , and , subunits, which specifically bind in a noncovalent interaction. Although the , chain remains on the cell surface, the , chain binds in an on-and-off interaction. Most anti-MUC1 antibodies (Abs) described to date recognize epitopes within the highly immunogenic ,-chain tandem repeat. Because the ,-chain is shed, such Abs are sequestered and fail to reach MUC1-expressing cells. Immunizing with cDNA encoding MUC1/TM and the spliced MUC1/X isoform from which the tandem repeat has been deleted yielded antibodies to the MUC1 ,/, junction. Pseudomonas toxin PE38 linked to polyclonal anti-MUC1 ,/, junction Abs both bound and killed MUC1-positive malignant cells. Monoclonal DMC209 binds the MUC1 ,/, junction in both MUC1/X and MUC1/TM. When injected into SCID mice xenotransplanted with human breast cancer MDA-MB-231, monoclonal DMC209 showed significant in vivo tumor-suppressive activity. The MUC1/X ,/, junction presents a biologically-significant target in MUC1-expressing malignancies because (i) antibodies directed against cell-bound ,/, junction epitopes reach the intended cellular target, (ii) antibodies to junction epitope are internalized into cells, (iii) anti ,/, junction antibodies can effectively kill high MUC1-expressing cancer cells as antibody-toxin conjugates and (iv) antibodies targeting the MUC1 cell-bound ,/, junction results in tumor suppression in vivo. Our results indicate that cell-bound MUC1 ,/, junction, unlike shed alpha chain, represents a highly effective moiety for targeting and killing MUC1-expressing malignancies. © 2008 Wiley-Liss, Inc. [source]

Astrocyte expression of a dominant-negative interferon-, receptor

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2005
Claudia Hindinger
Abstract Interferon-, (IFN-,) is a major proinflammatory cytokine, and binding to its nearly ubiquitous receptor induces a wide variety of biological functions. To explore the role(s) of IFN-, signaling in astrocytes, transgenic mice (GFAP/IFN-,R1,IC) expressing a dominant-negative IFN-, receptor alpha chain under control of the astrocyte-specific glial fibrillary acid protein (GFAP) promoter were generated. Transgenic mice developed normally, had normal astrocyte numbers and distribution, and exhibited no clinically overt phenotype. Transgene mRNA expression was detected only in the CNS, and the transgene-encoded IFN-, receptor 1 colocalized with GFAP, which is consistent with astrocyte expression. Astrocytes from transgenic mice exhibited reduced IFN-,-induced signaling as measured by major histocompatibility class II induction. Neither CNS inflammation nor perforin-mediated clearance of a neurotropic mouse hepatitis virus from astrocytes was impaired following infection. Transgenic mice with impaired astrocyte responsiveness to IFN-, provide a model for studying the selective astrocyte-dependent effects of this critical cytokine in CNS immunopathology. © 2005 Wiley-Liss, Inc. [source]

Comprehensive analysis of short peptides in sera from patients with IgA nephropathy

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 23 2009
Nagayuki Kaneshiro
We analyzed serum short peptides comprehensively to know whether they were useful to characterize IgA nephropathy (IgAN). Serum samples from 26 patients with untreated IgAN and 25 healthy donors were tested. Short peptides with molecular weights of ,7,kDa, purified from the serum samples by magnetic-beads-based weak cation exchange, were detected by mass spectrometry. Then the peptide peaks detected were subjected to the multivariate data analysis by SIMCA-P+® containing principal component analysis (PCA) and orthogonal partial-least-squares-discriminate analysis (OPLS-DA). A total of 92 peptide peaks were detected in the tested serum samples. The OPLS-DA analysis revealed that the profile of all the peptide peak intensities discriminated the IgAN group and the healthy group completely with a high R2 value (0.919) and a high Q2 value (0.861). Further, the profile of only five peptide peaks was found to discriminate the two groups. By tandem mass spectrometry and database searching, three of the five peptides which increased in the IgAN group were identified as fragments of fibrinogen alpha chain, and the two peptides which increased in the healthy group were identified as fragments of complement C3f and kininogen-1 light chain. Taken together, the profile of the serum short peptides would be useful to discriminate IgAN and healthy conditions. Further, the five peptides may be candidate serum markers for IgAN and may be related to pathogenesis of IgA. Copyright © 2009 John Wiley & Sons, Ltd. [source]