Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The synthetic peptide CKS-17 has homology to a highly conserved region of the immunosuppressive retroviral envelope protein P15E, to envelope proteins of HTLV I, II, III, and to that encoded by an endogeneous C-type human retroviral DNA. CKS-17 inhibits the immune response of lymphocytes and the respiratory burst of human monocytes. Because P15E-related antigens are present in human malignant cell lines and cancerous effusions, we sought to determine the effect of CKS-17 on monocyte-mediated tumor cell lysis. Lysis of A375 tumor cells by lymphokine or lipopolysaccharide-activated human monocytes was inhibited by 10 microM CKS-17 (control, 79%; CKS-17-treated, 19%). Another synthesized peptide, CS-2, which has partial homology to CKS-17, failed to block monocyte-mediated killing. Thus, the inhibition by CKS-17 appeared to be specific. Because interleukin 1 (IL-1) is a cytocidal factor produced by activated monocytes, we also investigated the effect of CKS-17 on IL-1 production by monocytes and on direct IL-1-mediated cytotoxicity. CKS-17 did not block production or secretion of IL-1 by lipopolysaccharide- or interferon-gamma-activated monocytes. However, the direct cytocidal activity of both recombinant IL-1 alpha and IL-1 beta against A375 tumor cells was blocked by CKS-17. The cytotoxic activity of IL-1 was inhibited by CKS-17 if (a) IL-1 was preincubated with CKS-17 for 1 hr at 37 degrees C or (b) the A375 cells were incubated with CKS-17 for 1 hr prior to the addition of IL-1. CKS-17 also blocked IL-1-induced proliferation of murine thymocytes, the D10 T cell line, and an IL-1-responsive astrocytoma cell line. These data suggest that CKS-17 may be a potent inhibitor of IL-1.
 ...
PMID:A synthetic peptide homologous to the envelope proteins of retroviruses inhibits monocyte-mediated killing by inactivating interleukin 1. 282 Nov 11

Preliminary experiments have suggested that guinea pig L2C B-cell leukemia cells were able to evade macrophage-mediated lysis. To determine whether the L2C cells were resistant to macrophage cytotoxic activity or whether factors associated with the L2C leukemia contributed to a generalized inhibition of macrophage cytotoxic activity, pulmonary macrophages from strain 2 guinea pigs with L2C leukemia were tested for their ability to lyse the susceptible K562 cell line after activation by lipopolysaccharide (LPS) or lymphokines. In addition, the potential presence of soluble inhibitors of macrophage tumoricidal activity in serum-free culture supernatants and in serum from strain 2 guinea pigs terminally ill with the leukemia was tested by determining the effects of leukemic guinea pig serum (LGPS) or L2C-conditioned medium (CM) on the tumoricidal activity of normal pulmonary macrophages. Macrophages from guinea pigs terminally ill with L2C leukemia were demonstrated to be depressed in their cytotoxic activity against the K562 cell after stimulation by either LPS or lymphokines when compared to normal macrophages. The lymphokine-stimulated cytotoxic activity of normal macrophages was inhibited in the presence of LGPS or CM. Oxidative burst activity of normal macrophages, as measured by zymosan-stimulated production of superoxide and hydrogen peroxide, was also inhibited under these conditions. The data presented here suggests that soluble factors associated with L2C leukemia cells can suppress oxidative burst activity of macrophages in vitro and that this effect may contribute to the ability of the leukemia cells to evade macrophage-mediated cytotoxicity.
 ...
PMID:Effects of L2C leukemia on macrophage-mediated responses. 282 44

Studies were made to determine whether freshly isolated monocytes from healthy donors could influence the induction of lymphokine (IL-2)-activated killer (LAK) activity. Highly purified lymphocytes (greater than 99%) and monocytes (greater than 90%) were isolated by counter-flow centrifugal elutriation from peripheral blood. Lymphocytes incubated for 4 days with IL-2 showed significant LAK activity against natural killer (NK) cell-resistant target (Daudi) cells, whereas monocytes treated for 4 days with IL-2 and/or IFN-gamma were not cytotoxic. Under the experimental conditions used, addition of monocytes to the lymphocyte cultures resulted in significant augmentation of the LAK activity, depending on the density of monocytes added. In contrast, monocytes stimulated by lipopolysaccharide (LPS) markedly suppressed LAK activity induced by IL-2, depending on the dose of LPS added. Similar up- and down-regulations of LAK cell induction by monocytes were observed with 4 lines of human lung cancer cells as targets for LAK activity. Although supernatants from untreated monocytes did not increase LAK induction, supernatants from LPS-stimulated monocytes suppressed LAK induction. The regulatory role of monocytes could not be replaced by the addition of exogenous interleukin I (IL-I) or tumor necrosis factor (TNF). Prostaglandin E did not seem to play a regulatory role, since addition of indomethacin did not affect the regulation of LAK cell induction by monocytes. These results clearly indicate that human monocytes may cause up- or down-regulation of the expression of IL-2-induced LAK activity, depending on their functional state.
 ...
PMID:Up- and down-regulation of human lymphokine (IL-2)-activated killer cell induction by monocytes, depending on their functional state. 282 45

Treatment of murine B cells with bacterial lipopolysaccharide (LPS) in the presence or absence of different lymphokines results in cell populations that differentially express particular immunoglobulin heavy chain constant region (CH) genes. This class switch involves recombination between switch regions located upstream of the germ-line CH genes. We have treated Abelson murine leukemia virus-transformed pre-B cells and normal splenic B cells with LPS or LPS plus the lymphokine IL-4 and examined the effect on the germ-line gamma 2b locus and gamma 2b class switching. In both cell types, LPS induces transcription specifically through the germ-line gamma 2b locus before gamma 2b class switching. Furthermore, IL-4 inhibits LPS induction of germ-line gamma 2b transcripts in spleen cells and correspondingly abrogates switching to this CH gene. Thus treatment with mitogens and lymphokines can alter transcription of germ-line CH genes in B lineage cells and thereby directly regulate class switching in the context of a recombinase accessibility mechanism.
 ...
PMID:Mitogen- and IL-4-regulated expression of germ-line Ig gamma 2b transcripts: evidence for directed heavy chain class switching. 283 63

Myoglobin-specific, Iad-restricted cloned helper T cells and T hybridomas were found to directly kill Iad-bearing, myoglobin-pulsed B lymphoma targets and could also kill bystander targets, but only in the presence of antigen-pulsed antigen presenting cells (APC). The induction of the killing requires recognition of processed antigen in the context of class II major histocompatibility complex (MHC) molecules. Despite the specificity of induction, the bystander killing suggests a nonspecific lytic mechanism. The direct killing can be inhibited only by cold specific targets, whereas the bystander killing can be blocked by both specific and nonspecific targets. The cold target inhibition seems to be due to interference with effector-to-target contact or proximity rather than due to high-dose suppression of T-cell activation. Experiments using T-cell supernatants or cyclosporin A suggested that the helper T cells kill targets by synthesizing short-range soluble factor(s) with nonspecific killing activity de novo during the effector phase, but only while antigen-specific signal transduction is occurring. The mechanism of cold target inhibition appears to be absorption or consumption of a short-acting cytotoxic lymphokine by cells which must be able to interact closely with the effector cell. Normal spleen B cells, despite their capability for activating the helper T cells, cannot inhibit specific killing or be killed by helper T cells, even after lipopolysaccharide stimulation. Thus, although killing by helper T cells may play a negative feedback role in the normal immune response, our data raise the possibility that the helper T-cell-mediated killing may contribute to the immune surveillance against malignancy by virtue of the preferential killing of tumor cells either directly or indirectly.
 ...
PMID:Cloned protein antigen-specific, Ia-restricted T cells with both helper and cytolytic activities: mechanisms of activation and killing. 295 81

Blast cell populations from 32 patients with acute non-lymphoblastic leukaemia of various morphological types have been examined for their ability to stimulate allogeneic T lymphocytes from normal donors in one-way mixed leucocyte culture (MLC). At the same time, these leukaemic cell populations were examined for the amounts of major histocompatibility complex Class I and Class II antigens they expressed, and their ability to release interleukin 1 (IL1) in culture both with and without stimulation by lipopolysaccharide. The abilities of the leukaemic cell populations to stimulate in MLC, and to produce IL1, were found to be associated with the expression of morphological characteristics of monocytic differentiation, and correlated significantly. In contrast, no correlation was observed between the extent of Class I or Class II expression and MLC stimulatory ability. Many myeloblast populations of immature phenotype were unable to stimulate allogeneic T cells despite their strong expression of these antigens. This lack of stimulatory ability was not overcome by the addition of exogenous IL1. We therefore conclude that the correlation between the production of IL1 and MLC stimulatory ability does not necessarily imply a cause/effect relationship, and that the interaction between allo-antigen and the T cell receptor together with a supply of lymphokine 'co-stimulator' is not sufficient to activate resting T lymphocytes. The failure of some Class I and II antigen positive leukaemic blasts to stimulate in MLC even in the presence of exogenous IL1 may be due to the lack of other differentiation-associated cell surface molecules necessary for stable cell-cell interaction.
 ...
PMID:Requirements for the stimulation of allogeneic T lymphocytes by acute non-lymphoblastic leukaemia cells. 296 Apr 48

Supernatants from a subset of helper T cell clones can enhance IgA, IgE, and IgG1 production in cultures of lipopolysaccharide-stimulated, T cell-depleted spleen cells. The lymphokine interleukin (IL)-4 has been shown to cause the IgE and IgG1 enhancement produced by these supernatants. IgA enhancement, however, is mediated by a factor distinct from IL-4, although IL-4 can potentiate the effect of the IgA-enhancing factor. IgA-enhancing factor is also distinct from IL-1, IL-2, IL-3, granulocyte-macrophage colony-stimulating factor, and interferon-gamma and acts directly on B cells. Purified IgA-enhancing factor enhances IgA production three- to sixfold yet causes less than a twofold increase in other isotypes. The IgA enhancing activity is not inhibited by concentrations of interferon-gamma that inhibit IL-4 activities. In the accompanying article, we show that this IgA enhancing activity is a novel property of the lymphokine IL-5.
 ...
PMID:A mouse T cell product that preferentially enhances IgA production. I. Biologic characterization. 296 Jul 39

Certain subsets of helper T cells, following stimulation with concanavalin A, secrete factors that specifically enhance the production of IgG1, IgE, and IgA by lipopolysaccharide-stimulated B cells. In the previous report, we describe a factor from the helper T cell line MB2-1 which enhances IgA production. IgA-enhancing factor has been purified from serum-free supernatants of this cell line. The purified lymphokine is a family of microheterogeneous polypeptides presumably modified post-translationally. IgA-enhancing factor has a native m.w. of 45,000 to 60,000 with subunits of between 24,000 and 28,000 under reducing conditions. Upon Edman degradation, a single amino-terminal sequence is detected which is identical to that of the lymphokine interleukin 5. IgA-enhancing factor activity is thus mediated by the same polypeptide that has been characterized as type II B cell growth factor, T cell-replacing factor, and eosinophil-differentiation factor.
 ...
PMID:A mouse T cell product that preferentially enhances IgA production. II. Physicochemical characterization. 296 Jul 40

An antiproliferative suppressor lymphokine was produced from rat T-cells specifically in response to the poorly immunogenic syngeneic mammary adenocarcinoma 13762A. The tumor-induced suppressor lymphokine (TISL) was produced late in culture (peak production on Days 4 and 5) and showed strong but selective inhibitory activity on a variety of immune responses. The immune peritoneal exudate cell response to a highly immunogenic clone from the parental tumor (clone 18A) and the concanavalin A-stimulated response of nonimmune spleen cells were inhibited strongly by TISL. In contrast, the immune spleen cell response to 13762A and the lipopolysaccharide response of nonimmume spleen cells were unaffected. Preliminary molecular weight and physicochemical analysis of TISL indicated that the molecule was large (Mr greater than 350,000); partially sensitive to 75 degrees C treatment for 15 min and to pH 2.0 treatment; only partly degraded by the enzymes trypsin, chymotrypsin, and proteinase K; and completely destroyed by boiling. Although TISL was produced specifically in response to 13762A tumor, prior immunization in vivo was not necessary for the induction of the suppressor lymphokine. These results indicate that populations of rat lymphocytes contain naturally occurring TISL secreting cells, which can be activated specifically by tumor antigens such as those expressed by 13762A.
 ...
PMID:Suppressor lymphokine produced by rat T-cells in response to syngeneic mammary adenocarcinoma 13762A. 296 35

Tumorilytic human blood monocytes recognize and destroy neoplastic cells by a mechanism that is nonphagocytic and requires cell-to-cell contact. The mechanism of cytolysis subsequent to binding is controversial. Release of reactive oxygen intermediates by activated rodent macrophages has been suggested as an important mechanism for tumor cell lysis in some short-term cytotoxicity assays. We examined whether oxygen intermediates are also responsible for mediating the lysis of adherent human tumor cells in a long-term (72-h) tumoricidal assay. Human blood monocytes were incubated with medium, concanavalin A-stimulated lymphokine [macrophage-activating factor (MAF)], lipopolysaccharide endotoxin, or human recombinant gamma interferon for 24 h prior to the addition of [125I] iododeoxyuridine-labeled A375 melanoma cells. The following evidence indicated that monocyte-mediated tumor cell lysis was independent of superoxide anion (O2-) and H2O2 production: (a) although human blood monocytes incubated for 24 h with gamma interferon produced twice as much O2- as control or MAF-treated monocytes, gamma interferon did not activate monocyte tumoricidal activity unless combined with lipopolysaccharide endotoxin, 0.2 ng/ml or more; (b) incubating the monocytes with 10 nM phorbol myristate acetate for 0.5 h stimulated O2- production but no cytotoxicity; (c) the cytolytic activity of MAF-treated monocytes was not decreased in the presence of catalase or superoxide dismutase; and (d) finally, peripheral blood monocytes were isolated from six patients with chronic granulomatous disease, activated by MAF or lipopolysaccharide endotoxin, and then assayed for tumoricidal activity. While these activated chronic granulomatous disease monocytes did not produce O2- or H2O2, tumor cell lysis was normal in all six patients. Hence, lysis of tumor cells in a 72-h assay is not dependent upon the generation of O2- and/or H2O2 and is intact in chronic granulomatous disease monocytes.
 ...
PMID:Lysis of tumor cells by human blood monocytes by a mechanism independent of activation of the oxidative burst. 298 42


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>