[Show abstract][Hide abstract] ABSTRACT: Sarcolectin (SCL) is a nonspecific stimulator of cellular DNA synthesis that was found in all animal sera tested to date. It inhibits the established interferon (IFN)-dependent antiviral state, restoring cells to their normal status. In this study, we examined the excretion/secretion of the IFN antagonist SCL in sera from healthy donors and in sera collected during different periods of human immunodeficiency virus type 1 (HIV-1) infection. We followed HIV-1-infected patients during all stages of development (seroconversion, initial and advanced phases of AIDS) and found a significant increase in SCL in sera of HIV-infected patients compared with seronegative subjects used as controls. This increase was established during seroconversion, and then the titers leveled off. In the final stage of the disease, the SCL titer increased again very significantly. We attribute this rapid rise to the virus-dependent destruction of T cells that can no longer be repaired. The high SCL level observed at this final stage, which is most predictive of the disease's progression, suggests that the action, rather than the production, of IFN is impaired.
Journal of Interferon & Cytokine Research 04/2002; 22(3):305-10. DOI:10.1089/107999002753675721 · 3.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: a a b b a The aim of this study was to investigate the involvement of sarcolectin in HIV-1 pathogenesis. During the infection and during progression of the disease the immune functions are indeed repeatedly challenged. We studied the presence of sarcolectin in three cohorts. Two were HIV-infected patients randomly selected at different phases of the disease as indicated: (a) controls; (b) seroconverted or early phase of AIDS (Centers for Disease Control and Prevention (CDC) I/II); (c) advanced AIDS (CDC III) generalized lymphadenopathy with or without common symptoms (CDC IV) opportunistic infections or secondary tumours were studied. Our results indicated that sarcolectin was overproduced in sera from AIDS patients compared with sera from control donors. Statistical calculations using regression coefficients showed a significant increase of sarcolectin titres in sera: between (a)/(b) t: 6,32; (a)/(c) t: 9,77; (b)/(c) t: 10,21. In all groups < 0.001(). Moreover, Western blotting assays showed that more sarcolectin was produced in sera in advanced cases of AIDS when compared with controls (results not shown). (6,7)
AIDS 09/2000; 14(14). DOI:10.1097/00002030-200009290-00020 · 6.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: T cell multiplication is attributed to the growth factor interleukin-2 (IL-2), which is, however, only activated when a specific cell membrane-bound receptor can be expressed. We found in all human sera tested a lectin that we described and called sarcolectin (SCL). SCL is a molecularly cloned 55-kDa protein that stimulates DNA synthesis in all immunocompetent cells and inhibits the interferon (IFN)-dependent antiviral state. SCL is excreted in conditioned medium of T cell cultures grown under serum-free conditions, where it can be demonstrated regularly by Western blots. In such cultures, in addition to SCL and IL-2, IFN-gamma and IFN-alpha also can be found, likely as a feedback response to DNA stimulation. Considered together, the data suggest that coordinated clonal expansion of T cells is governed by SCL-IL-2, both which induce T cell proliferation and simultaneously activate IL-2 receptors. T cell replication is downregulated by the effect of feedback IFN-gamma and IFN-alpha. To initiate a new growth cycle, SCL is thought to block the residual IFN-dependent antiproliferative state.
Journal of Interferon & Cytokine Research 06/2000; 20(5):519-25. DOI:10.1089/10799900050023942 · 3.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Interferons (IFNs) are major cytokines, responsible for down-regulating cell growth and for promoting cell differentiation. The sarcolectin (SCL) protein presented here blocks in the cells the established IFN-dependent interphase and stimulates DNA synthesis, probably in co-ordination with more specific growth factors or hormones. The SCL-DNA structure is closely related to that of cytokeratine K2C7 intermediate filaments, but the SCL is a monomer, or sometimes a dimer, which is excreted into the serum, where it is frequently bound to albumin. Its specific biological functions are carried by the beta sheets, and can be found on the two terminal domains of the molecule, the lectinic properties being located mainly on the N-terminus. The recombinant SCL molecule possesses the same biological functions as the native one, since it inhibits the IFN-dependent antiviral state both in human and in mouse cell cultures. On the contrary, antibodies raised against amino acids 41-55 located on the N-terminal domain of SCL inhibit this antagonistic effect. We postulate that the IFN and SCL proteins, because of their opposite biological functions, are in balance and are part of a feedback system operating the regulation of normal growth. In pathological cases, SCL could play a role in the development of tumors, as we have found in juvenile osteosarcomas or in AIDS cases.
[Show abstract][Hide abstract] ABSTRACT: We have reported previously that Moloney virus-transformed cells, when treated for over 200 passages in the presence of low concentrations of mouse interferon-alpha/beta, can be reverted to a stable nonmalignant status. The cells recover full contact inhibition and are unable to raise tumors when grafted in nude mice. In the present report, we show that whether reverted or malignant, these cells contain deleted v-mos oncogenes, which have lost 392 nucleotides. The truncated oncogenes contain a reduced and modified open reading frame but are able, however, to induce tumors when transfected in mouse 3T3 cells. As there is no difference either in the location or in the structure of this modified v-mos, whether yielded by reverted or malignant cells, we postulate that both cell lines derive from the same population and this modification does not play any role in the reversion process obtained through prolonged IFN-dependent selection. We suggest that reversion could be an epigenetic phenomenon, involving the constitutive synthesis of IFN-beta only in the reverted and not in the malignant cells. The continued persistence of such noncancerous cells could result at least partly from a balance involving the expression of v-mos, IFN-beta, and an IFN antagonist, sarcolectin. These reverted cells can undergo an unlimited number of passages, but they must be trypsinized before day 5 in confluent cultures. Thereafter, the cells stop dividing, cannot proliferate anymore, progressively show signs of apoptosis, and die.
Journal of Interferon & Cytokine Research 01/1998; 17(12):739-46. DOI:10.1089/jir.1997.17.739 · 3.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prolonged interferon (IFN) treatment can convert Moloney sarcoma-transformed mouse Balb C fibroblasts to a stable non-malignant status. The cells recover a number of differentiated features, which are maintained even when IFN is permanently omitted from the tissue culture medium. We show here that reversion could be at least in part attributed to constitutive IFN beta synthesized only in the reverted cells. The continued replication of these cells, although unable to induce tumours in athymic mice, could be the result of the maintained expression of an IFN antagonist termed sarcolectin (SCL), a balance being struck between the effects of v-mos oncogene, interferon beta and SCLs. In agreement with Lampl et al. , we suggest that normal cell growth is discontinuous, consisting of sudden bursts followed by prolonged arrests which could be necessary to promote differentiation during the ensuing interphase.
Comptes Rendus de l Académie des Sciences - Series III - Sciences de la Vie 12/1993; 316(11):1286-9.