scholarly journals Lamina propria macrophages in the human gastrointestinal mucosa: their distribution, immunohistological phenotype, and function.

1996 ◽  
Vol 44 (7) ◽  
pp. 721-731 ◽  
Author(s):  
R Nagashima ◽  
K Maeda ◽  
Y Imai ◽  
T Takahashi
Keyword(s):  
Epithelial Cell ◽  
Lamina Propria ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Double Staining ◽  
Gastrointestinal Mucosa ◽  
Double Positive ◽  
Cellular Debris ◽  
And Function

In this study we systematically investigated the cellular distribution, immunohistochemical phenotype, and mucosal disposal function of macrophages in the lamina propria of the human gastrointestinal mucosa (lamina propria macrophages; LPMs). In all tissues examined, most of these LPMs accumulated beneath the epithelial layer that covered the apex of the lamina propria of the mucosa. These cells expressed normal levels of common macrophage markers such as CD68, LN5, lysozyme, ferritin, and alpha 1-anti-chymotrypsin. In addition, they expressed high levels of 25F9 (a market for a certain subpopulation of macrophages), MHC Class II molecules, and CD74 (MHC Class II-associated invariant chain). Interestingly, LPMs possessed some epithelial cell-associated antigens such as cytokeratin, carcinoembryonic antigen (CEA), and Ber-Ep4 in their cytoplasm. Ultrastructurally, these antigens were associated with cellular debris ingested by LPMs, which were recognized as apoptotic fragments by in situ end-labeling. Furthermore, double positive-labeled granules were seen in LPMs by double staining for epithelial cell-associated antigens and in situ end-labeling. These observations suggest that one of the major functions of LPMs is the disposal of apoptotic epithelial cells and that LPMs may be involved in the regulation of mucosal epithelial renewal.

scholarly journals Modulation of Major Histocompatibility Class II Protein Expression by Varicella-Zoster Virus

2000 ◽  
Vol 74 (4) ◽  
pp. 1900-1907 ◽  
Author(s):  
Allison Abendroth ◽  
Barry Slobedman ◽  
Eunice Lee ◽  
Elizabeth Mellins ◽  
Mark Wallace ◽  
...  
Keyword(s):  
Cell Surface ◽  
Varicella Zoster Virus ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Northern Blot Hybridization ◽  
Major Histocompatibility ◽  
Varicella Zoster ◽  
Ifn Γ ◽  
In Cells

ABSTRACT We sought to investigate the effects of varicella-zoster virus (VZV) infection on gamma interferon (IFN-γ)-stimulated expression of cell surface major histocompatibility complex (MHC) class II molecules on human fibroblasts. IFN-γ treatment induced cell surface MHC class II expression on 60 to 86% of uninfected cells, compared to 20 to 30% of cells which had been infected with VZV prior to the addition of IFN-γ. In contrast, cells that were treated with IFN-γ before VZV infection had profiles of MHC class II expression similar to those of uninfected cell populations. Neither IFN-γ treatment nor VZV infection affected the expression of transferrin receptor (CD71). In situ and Northern blot hybridization of MHC II (MHC class II DR-α) RNA expression in response to IFN-γ stimulation revealed that MHC class II DR-α mRNA accumulated in uninfected cells but not in cells infected with VZV. When skin biopsies of varicella lesions were analyzed by in situ hybridization, MHC class II transcripts were detected in areas around lesions but not in cells that were infected with VZV. VZV infection inhibited the expression of Stat 1α and Jak2 proteins but had little effect on Jak1. Analysis of regulatory events in the IFN-γ signaling pathway showed that VZV infection inhibited transcription of interferon regulatory factor 1 and the MHC class II transactivator. This is the first report that VZV encodes an immunomodulatory function which directly interferes with the IFN-γ signal transduction via the Jak/Stat pathway and enables the virus to inhibit IFN-γ induction of cell surface MHC class II expression. This inhibition of MHC class II expression on VZV-infected cells in vivo may transiently protect cells from CD4+ T-cell immune surveillance, facilitating local virus replication and transmission during the first few days of cutaneous lesion formation.

Erythropoietin as a Novel Pro-Inflammatory Mediator of Macrophages.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3596-3596
Author(s):  
Lilach Lifshitz ◽  
Galit Tabak ◽  
Max Gassman ◽  
Moshe Mittelman ◽  
Drorit Neumann
Keyword(s):  
Mhc Class Ii ◽  
Phagocytic Activity ◽  
Surface Expression ◽  
Class Ii ◽  
Experimental Models ◽  
Splenic Macrophage ◽  
And Function ◽  
Inflammatory Macrophages

Abstract Abstract 3596 Poster Board III-533 The immunomodulatory effects of erythropoietin (EPO) on the cellular and humoral compartments of the immune system were originally described by our group in multiple myeloma patients and have been further elucidated in murine experimental models (Mittelman, 2001; Katz 2005; 2007; Prutchi-Sagiv, 2006). However, the mechanisms of action by which EPO affects lymphocyte number and function are still unknown, particularly since lymphocytes do not carry EPO receptors (EPO-R). We thus set to unravel mechanisms underlying the anti-neoplastic immunomodulatory action of EPO. These studies led us to the novel discovery that dendritic cells (DCs) express EPO-R, and that EPO enhances their survival and function (Prutchi-Sagiv, 2008; Lifshitz, 2009). Here we focus on macrophages as an additional EPO target, since in analogy to DCs, macrophages are also antigen presenting cells, and serve as key effectors of the innate immune response. Using murine models, we first explored the in-vivo effects of EPO using recombinant human EPO (rHuEPO, EPREXR, JC)-injected mice, as well as transgenic mice over-expressing human EPO (termed tg6). EPO treatment was associated with an increased splenic macrophage population, detected by F4/80 expression, and an increased number of macrophages expressing CD11b, CD80 and MHC class II. We further explored the effect of in-vivo EPO administration in an inflammatory model exploiting thioglygollate injection to induce recruitment of peritoneal inflammatory macrophages. The inflammatory macrophages obtained from both EPO injected and from tg6 mice displayed increased expression of F4/80, CD11b, CD80 and MHC class II and augmented phagocytic activity, as compared to the control counterparts. These results are supported by in-vitro studies in bone marrow derived macrophages (BMDMs). We show that BMDMs express EPO-R mRNA, as detected by RT-PCR. In-vitro stimulation of the BMDMs with rHuEPO activated multiple signaling pathways including STAT1, STAT5, MAPK, AKT and NFkB indicating macrophage activation via surface EPO-R. EPO treatment of the BMDMs up-regulated their surface expression of CD11b, F4/80 and CD80, as well as enhanced their phagocytic activity. EPO treatment of LPS-stimulated BMDMs augmented IL-12 secretion, and decreased IL-10 secretion. In conclusion our results show that macrophages are direct targets of EPO and that EPO treatment enhances their pro-inflammatory activity and function. These findings point to the multifunctional role of EPO and may advance its clinical applications as an anti-neoplastic immunomodulator. Disclosures: Mittelman: BioGAL- Start up (inactive): Equity Ownership, Patents & Royalties. Off Label Use: Non erythroid effects: immune, anti-cancer (all under investigation).

Molecular structure and function of CD4 on murine egg plasma membrane

Zygote ◽  
1995 ◽  
Vol 3 (1) ◽  
pp. 65-73 ◽  
Author(s):  
Mao Wu Guo ◽  
Toshiki Watanabe ◽  
Etsuko Mori ◽  
Tsuneatsu Mori
Keyword(s):  
Plasma Membrane ◽  
Mhc Class Ii ◽  
Expression System ◽  
Direct Interaction ◽  
Baculovirus Expression System ◽  
Class Ii ◽  
Sf9 Cells ◽  
Sperm Cells ◽  
Nuclear Polyhedrosis ◽  
And Function

SummaryIn the present study, the expression of the CD4 molecule on murine egg plasma membrane was confirmed by the indirect immunofluorescence (IIF) method. The full-length CD4 cDNA from murine eggs was synthesised by the reverse transcriptase-polymerase chain reaction (RT-PCR) method and its authenticity verified by Southern blot hybridisation using an end-labelled internal oligonucleotide. The results of DNA sequencing showed that the nucleotide sequence of the cDNA of CD4 from murine egg mRNA was identical to that of immune T cells. To demonstrate the direct interaction of CD4 from murine egg with murine sperm cells bearing MHC (major histocompatibility complex) class II molecule, we employed a baculovirus expression system to generate CD4 on the surface of Spodoptera frugiperda (Sf9) cells. Expression of CD4 on Sf9 cells infected with autographa californica nuclear polyhedrosis virus (AcNPV)-CD4 was demonstrated by IIF and immunoblotting. The CD4-expressing Sf9 cells adhered to MHC class II-bearing sperm cells since the adhension was specifically blocked by anti-CD4 monoclonal antibody (mAb) or anti-monomorphic region of MHC class II mAb. Taking our previous and present experimental results together, they strongly suggest that intercellular membrane adhesion between two gametes at the fusion step in fertilisation is mediated by the MHC class II molecule located on the posterior region of the sperm head and the CD4 molecule on egg plasma membrane.

scholarly journals The invariant chain is required for intracellular transport and function of major histocompatibility complex class II molecules.

1994 ◽  
Vol 179 (2) ◽  
pp. 681-694 ◽  
Author(s):  
E A Elliott ◽  
J R Drake ◽  
S Amigorena ◽  
J Elsemore ◽  
P Webster ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Intracellular Transport ◽  
Class Ii ◽  
Misfolded Proteins ◽  
Invariant Chain ◽  
Major Histocompatibility ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
And Function

The major histocompatibility complex (MHC) class II-associated invariant chain (Ii) is thought to act as a chaperone that assists class II during folding, assembly, and transport. To define more precisely the role of Ii chain in regulating class II function, we have investigated in detail the biosynthesis, transport, and intracellular distribution of class II molecules in splenocytes from mice bearing a deletion of the Ii gene. As observed previously, the absence of Ii chain caused significant reduction in both class II-restricted antigen presentation and expression of class II molecules at the cell surface because of the intracellular accumulation of alpha and beta chains. Whereas much of the newly synthesized MHC molecules enter a high molecular weight aggregate characteristic of misfolded proteins, most of the alpha and beta chains form dimers and acquire epitopes characteristic of properly folded complexes. Although the complexes do not bind endogenously processed peptides, class II molecules that reach the surface are competent to bind peptides added to the medium, further demonstrating that at least some of the complexes fold properly. Similar to misfolded proteins, however, the alpha and beta chains are poorly terminally glycosylated, suggesting that they fail to reach the Golgi complex. As demonstrated by double label confocal and electron microscope immunocytochemistry, class II molecules were found in a subcompartment of the endoplasmic reticulum and in a population of small nonlysosomal vesicles possibly corresponding to the intermediate compartment or cis-Golgi network. Thus, although alpha and beta chains can fold and form dimers on their own, the absence of Ii chain causes them to be recognized as "misfolded" and retained in the same compartments as bona fide misfolded proteins.

Turning tumor cells in situ into T-helper cell-stimulating, MHC class II tumor epitope-presenters: immuno-curing and immuno-consolidation

2004 ◽  
Vol 30 (3) ◽  
pp. 281-290 ◽  
Author(s):  
Gilda G Hillman ◽  
Nikoletta L Kallinteris ◽  
Xueqing Lu ◽  
Yu Wang ◽  
Jennifer L Wright ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Mhc Class Ii ◽  
Class Ii ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper

scholarly journals Efficient loading of identical viral peptide onto class II molecules by antigenized immunoglobulin and influenza virus.

1993 ◽  
Vol 178 (5) ◽  
pp. 1795-1799 ◽  
Author(s):  
T D Brumeanu ◽  
W J Swiggard ◽  
R M Steinman ◽  
C A Bona ◽  
H Zaghouani
Keyword(s):  
Influenza Virus ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Mhc Molecules ◽  
Influenza Virus Hemagglutinin ◽  
Mhc Class Ii Antigens ◽  
Efficient Loading ◽  
Class Ii Antigens ◽  
Mhc Class Ii Molecules

Several prior reports have identified peptides that are naturally associated with major histocompatibility complex (MHC) class II molecules on presenting cells. We have examined the delivery of a peptide from exogenous sources to MHC class II molecules. The peptide derives from the influenza virus hemagglutinin (HA) and activates a CD4+ T cell hybridoma. In functional assays of antigen presentation, this epitope is delivered effectively to T cells either in the context of influenza virus or chimeric immunoglobulin (Ig) molecules (Ig-HA) in which the peptide has replaced the CDR3 loop of the heavy chain. We find that the identical 11-mer peptide can be isolated from mouse MHC class II antigens whether the exogenous source of peptide is free HA peptide, the Ig-HA chimera, or ultraviolet-inactivated PR8 influenza virus. The Ig-HA chimera proves to be the most efficient vehicle for charging class II molecules via the exogenous route. Given the fact that self Igs represent natural long-lived carriers, we suggest that antigenized Igs have considerable potential for peptide delivery to MHC molecules in situ.

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