Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Membrane cofactor protein (MCP, CD46) of the complement system is a measles virus (MV) receptor. Human lymphocytes express a heavily glycosylated (H) and a lightly glycosylated (L) form of MCP, which confers a two-band profile on SDS-PAGE the ratio of which is controlled genetically and organ-specifically. In contrast, granulocytes express a single heavily glycosylated form regardless of lymphocyte MCP phenotype. We investigated susceptibility to MV of granulocytes and lymphocytes from individuals with different lymphocyte MCP phenotypes. In any individual, granulocytes were > 10-fold less susceptible to MV than lymphocytes, and the lymphocytes with predominant H form were generally less susceptible to those with an increasing amount of L form. Thus, lymphocytes always exhibit high susceptibility to MV compared to granulocytes in all individuals. This finding may explain the lymphopenia and immunosuppression observed secondary to MV infection.
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PMID:Human lymphocytes are more susceptible to measles virus than granulocytes, which is attributable to the phenotypic differences of their membrane cofactor protein (CD46). 871 5

During measles virus (MV) infection, lymphopenia and immune suppression are observed in humans, yet the mechanisms underlying these effects remain unknown except that membrane cofactor protein (MCP, CD46) acts as a receptor for MV, accelerating entry of the virus into host cells. CD46 is a complement regulator, the role of which is to protect host cells from the autologous complement system. Thus, it encompasses complement-related and MV-mediated immune modulation. In this review, I discuss the structural and functional differences between CD46 on lymphocytes and on granulocytes, which partly explain the higher susceptibility of lymphocytes to MV than other blood cells to clarify the mechanisms of MV-mediated lymphopenia and immune suppression, and help resolve the T cell immunity dysfunction secondary to virus infection including HIV.
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PMID:CD46, a complement regulatory protein/measles virus receptor, and its relation to hematological disorders. 885 67

Morbilliviruses are highly contagious pathogens that cause some of the most devastating viral diseases of humans and animals, including measles virus (MV), canine distemper virus (CDV), and rinderpest virus (RPV). They replicate mainly in lymphoid organs throughout the body and cause severe immunosuppression accompanied with lymphopenia. We have recently shown that human, canine, and bovine signaling lymphocyte activation molecules (SLAMs; also known as CD150) act as cellular receptors for MV, CDV, and RPV, respectively. In these three morbilliviruses, all strains examined were shown to use SLAMs of their respective host species, and laboratory strains passaged on SLAM-negative cells were found to use, besides SLAM, alternative receptors, such as human CD46 for the Edmonston strain of MV. The use of SLAM as a receptor may be a property common to most, if not all, of the members of morbilliviruses. Human SLAM is a membrane glycoprotein selectively expressed on the cells of the immune system (immature thymocytes, activated lymphocytes, activated monocytes, and mature dendritic cells) and seems to mediate lymphocyte activation and to control interferon-gamma production. The destruction and/or impairment of infected SLAM-positive cells may be a mechanism for the immunosuppression induced by morbilliviruses, but other mechanisms may be also involved.
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PMID:The morbillivirus receptor SLAM (CD150). 1200 21

Although MV infection causes lymphopenia and degradation of cell-mediated immunity, the mechanisms are poorly known. MV interacts with cellular receptors which mediate virus binding and uptake and are on the surface of PBMC. In this study, apoptosis of MV-infected PBMC in vitro was analyzed. Both PBMC treated with UV-inactivated viruses and those infected with live MV underwent apoptosis. Apoptosis of wild-type MV-infected PBMC was blocked by anti-SLAM and anti-MV hemagglutinin antibodies, respectively. Furthermore, addition of soluble MV hemagglutinin recombinant protein induced apoptosis in PBMC. These data suggest that induction of apoptosis in MV-infected PBMC is triggered by interaction between hemagglutinin protein of MV and receptor, without other viral components. To further determine the mechanisms of apoptosis, caspase activity was analyzed by Western blotting. Wild-type virus Yonekawa strain-induced apoptosis was blocked by pretreatment with pan-caspase inhibitor (Z-VAD-fmk). Intriguingly, the laboratory-adapted Nagahata strain-induced apoptosis was not blocked by Z-VAD-fmk, indicating that there may be different apoptosis pathways which depend on the viral receptors, SLAM and CD46. Both extrinsic and intrinsic apoptotic pathways, including activation of caspase-3, -8 and -9, are involved in Yonekawa strain-induced apoptosis. Taken together, the findings of this study could open up a new avenue for understanding the molecular mechanisms of MV-induced PBMC apoptosis and immunosuppression.
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PMID:Apoptosis of human peripheral blood mononuclear cells by wild-type measles virus infection is induced by interaction of hemagglutinin protein and cellular receptor, SLAM via caspase-dependent pathway. 2061 87

CD55, CD59, CD46, and CD35 are proteins with complement regulatory (Creg) properties that ensure cell and tissue integrity when this system is activated. The aim of this study was to evaluate the Creg expression on peripheral blood cells from SLE patients and its association with cytopenia and disease activity. Flow cytometric analyses were performed on blood cells from 100 SLE patients and 61 healthy controls. Compared with healthy controls, we observed in SLE patients with lymphopenia and neutropenia decreased expression of CD55, CD59, and CD46 (P < 0.05). In SLE patients with anemia, CD59 and CD35 were decreased on red blood cells. Furthermore, there was a negative correlation between CD55 and CD59 on neutrophils and the disease activity. The results suggest there is an altered pattern of Creg expression on the peripheral blood cells of SLE patients, and the expression is correlated with disease activity and/or with activation of the complement system.
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PMID:Diminished expression of complement regulatory proteins on peripheral blood cells from systemic lupus erythematosus patients. 2276 33