Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The complement (C) system has previously been implicated in several diseases of muscle. We here report that human myoblasts or rhabdomyosarcoma cell lines spontaneously activate C through the classical pathway, causing release of anaphylatoxins and coating of myoblasts with opsonic C fragments but without causing cell killing. Survival of myoblasts is a consequence of the abundant expression of the membrane C regulatory molecules MCP and CD59, and neutralization of CD59 renders cells susceptible to C killing. The decay-accelerating factor was expressed at a very low level. Myoblasts and rhabdomyosarcoma lines also abundantly express the fluid-phase regulators C1-inhibitor, factor H, C4 binding protein, S-protein, and clusterin and secrete a soluble form of CD59. Expression of membrane and fluid-phase regulators is enhanced by either IFN-gamma or TNF-alpha. Although myoblasts resist C killing, spontaneous activation of C on these cells may have important consequences in inflammatory diseases of muscle where the generation of anaphylactic and opsonic fragments will recruit and activate inflammatory cells. C activation on myoblasts may also have consequences for the use of these cells as vehicles for gene delivery. Inhibition of C using soluble complement receptor I (sCR1) efficiently protected myoblasts from C attack in vitro, and this agent, already being tested in therapy of several C-mediated diseases, might be of value in inflammatory muscle disease and in improving the efficiency of gene delivery.
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PMID:Human skeletal myoblasts spontaneously activate allogeneic complement but are resistant to killing. 861 66

Previously we showed for coxsackievirus A9 (CAV-9) that specific interactions between the RGD motif of capsid protein VP1 and the alpha v beta 3 integrin are involved in virus binding and entry into green monkey kidney cells (GMK) and some other cell lines. The RGD-recognizing alpha v beta 3 integrin is known as the vitronectin receptor (VNR). During replication in the gut, CAV-9 like all other enteroviruses are exposed to host proteolytic enzymes, and we showed previously that the RGD-containing 15 amino acids long carboxy terminal extension of VP1 is cleaved off by trypsin. The trypsin-treated CAV-9 was still infectious, although at an apparently reduced level as assessed in GMK cells. This indicated that the virus was able to bypass the RGD-dependent entry and possibly use an alternative receptor. We have now found that in RD cells, a human rhabdomyosarcoma cell line, neither RGD-containing oligopeptides nor polyclonal antiserum to VNR are able to protect the cells from CAV-9 infection suggesting that the RGD motif is not involved in binding or entry of the virus into these cells. This result was further confirmed by demonstrating that, in RD cells, the trypsin-treated CAV-9 lacking the RGD-containing insert appeared to be as infectious as the untreated virus. The most striking difference between the virus receptors in the RD and the GMK cells was seen when the rate of virus uncoating was studied. For virus particles bound to the RD cells, the uncoating step started already at 18-20 degrees C and the process went on rapidly at 36 degrees C resulting in complete disintegration of cell-bound virions. In contrast, alpha v beta 3-bound virus particles in the GMK cells appeared to uncoat slowly even at 36 degrees C and during the 90 min observation period only a small, hardly visible fraction was found to be disintegrated. Trypsin-cleaved CAV-9 showed the rapid disintegration kinetics in GMK cells as well suggesting that these cells contain both types of receptor specificity. These results indicate that CAV-9 is able to use two different entry routes into host cells depending on the target cells and on phenotypic properties of the virus regulated by host proteases.
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PMID:Efficient RGD-independent entry process of coxsackievirus A9. 892 Aug 24