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

Human C1 inhibitor (C1 INH) enhances the chemotactic responsiveness of human leukocytes to lipopolysaccharide (LPS), AgAb complex, and zymosan-activated plasma or serum when added to the compartment of the chemotaxis chamber containing the cells. It seems to affect cells directly and causes an increased number of leukocytes to respond to the chemotactic factors at early time intervals. Spontaneous motility does not appear to be affected. Results of studies employing anti-C3 and anti-C5 sera seem to indicate that the chemotactic factor derived from C5 is involved in the C1 INH induced enhancement of chemotaxis. In fact, preliminary experiments utilizing trypsinactivated C3 as a chemotactic source indicate that C1 INH causes inhibition of chemotactic response to C3a. C1 INH is the first naturally occurring plasma component reported to cause enhanced chemotactic responsiveness.
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PMID:Effects of human C 1 inhibitor on complement-mediated human leukocyte chemotaxis. 116 60

The ability of human peripheral blood monocytes to secrete plasma serine protease inhibitors was studied. Monocytes from blood obtained from healthy young adult volunteers were cultured for up to 36 h with and without lipopolysaccharide from Escherichia coli. The concentrations of plasma serine protease inhibitors in monocyte culture supernatants were measured by using rocket immunoelectrophoresis. The study showed that human monocytes stimulated with lipopolysaccharide in vitro release antithrombin III, C1 esterase inhibitor, alpha 2-antiplasmin, and alpha 2-macroglobulin.
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PMID:Human monocytes release plasma serine protease inhibitors in vitro. 170 Jul 59

The dose and time dependence of endotoxin-induced activation of the plasma contact system have been studied. Citrated pool plasma was incubated at 37 degrees C with endotoxin doses of 2.10(5), 2.10(6), 2.10(7), and 2.10(9) ng/l (lipopolysaccharide B, E. coli 026: B6, Difco Laboratories, Detroit, MI) for 24 hr. Samples for determination of components of the contact system were obtained prior to incubation and at 1, 2, 4, 6, 12, and 24 hr. Plasma kallikrein (KK) activity markedly increased at 12 hr in test plasma containing the highest dose of endotoxin (2.10(9) ng/l). Coincident with the elevated KK activity, reductions of both plasma prekallikrein (PKK) and functional kallikrein inhibition (KKI) were seen as assayed by chromogenic peptide substrate analyses. Also, functionally determined alpha 2-macroglobulin (alpha 2-M) and C1 inhibitor (C1INH) values were decreased, confirming the reduction of KKI values. Changes of Hageman factor (FXII), PKK, and high molecular weight kininogen (HMWK) values were also found at the same time point when assayed by immunochemical techniques. The same pattern of changes was seen in test plasma containing 2.10(7) and 2.10(6) ng/l of endotoxin. These changes, however, were less pronounced and not seen until 24 hr after beginning incubation. In control plasma and in plasma containing the lowest dose of endotoxin (2.10(5) ng/l), no changes were seen in any factors of the contact system. Our study shows that in vitro endotoxin-induced activation of the contact system is a slow process that is both time and dose dependent.
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PMID:Dose dependence of endotoxin-induced activation of the plasma contact system: an in vitro study. 246 83

The effects of methylprednisolone sodium succinate (MP) on main inhibitors of the classical pathway of complement and on the contact system were studied in citrated pool plasma. Endotoxin (2.10(9) ng/l, lipopolysaccharide B, E. coli 026: B6 Difco Laboratories, Detroit, Michigan, USA) and/or MP in doses of 0.1, 1, 5 and 10 mg/ml were incubated with plasma at 37 degrees C. Plasma samples were obtained at timed intervals up to 24 hours for determination of C1 inhibitor (C1inh) and alpha 2-macroglobulin (alpha 2M) values using both functional and immunochemical assays. Plasma containing endotoxin without MP revealed decreases of C1inh and alpha 2M values after 12 hours. Addition of MP in high doses (10 mg/ml) gave an additive effect on the endotoxin-induced decreases of C1inh and alpha 2M values, evident 1 and 12 hours after the beginning of incubation, respectively. When MP alone was added to plasma (5 and 10 mg/ml) also significant decreases in C1inh and alpha 2M values were seen. MP in low doses (0.1 and 1 mg/ml) did not either influence the endotoxin-induced changes in the protease inhibitor functions, or induce significant changes in C1inh and alpha 2M values when incubated in plasma without endotoxin. This study demonstrates that MP in high doses induces marked decreases in plasma C1inh and alpha 2M inhibitory functions and that MP has an additive effect on the endotoxin-induced decreases of these inhibitors.
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PMID:Methylprednisolone affects inhibitors of the complement and the contact systems; functional and immunochemical studies on alpha 2-macroglobulin and C1 inhibitor. 248 62

C1 inhibitor (C1INH) is the major control factor for the activation of the classical pathway of complement and for contact system activation. Hepatocytes and blood monocytes are known to synthesize this protease inhibitor. We studied the regulation of monocyte C1INH production by mediators that are generated during inflammatory responses. Purified blood monocytes spontaneously synthesized and secreted C1INH only after prolonged culture. In the presence of interferon (IFN)-gamma, C1INH was detectable within 24 hr and continued to be released at high levels throughout an 8-day culture period. Monocyte C1INH was newly synthesized and was functionally active as determined by forming stable complex with C1s. Other monocyte stimuli were either less potent (IFN-alpha, IFN-beta) or not capable of increasing C1INH release (lipopolysaccharide, interleukin 1, and tumor necrosis factor). The second component of complement, C2, was induced by IFN-gamma to a similar extent as C1INH. These findings demonstrate that IFN-gamma is a major regulator of monocyte C1INH production and may warrant consideration of IFN-gamma in the treatment of C1INH deficiency states.
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PMID:Interferon-gamma is a major regulator of C1-inhibitor synthesis by human blood monocytes. 311 6

The purpose of this study was to find whether a glycerolphosphate-containing lipoteichoic acid prepared from Streptococcus sobrinus OMZ 176 cells would activate the classical pathway of complement while in solution. Reference activators were lipopolysaccharide from Escherichia coli 0111:B4 and heat-aggregated immunoglobulin G. Serum samples were taken from healthy students. Analysis through crossed immunoelectrophoresis showed that lipoteichoic acid caused an almost complete dissociation of the C1qrs macromolecule. All activators decreased the area of and slowed the electrophoretic mobility of the C4 protein peaks, with lipoteichoic acid causing the most pronounced alterations. Electroimmunoassays showed that lipoteichoic acid separately, yielded detectable amounts of free C1r2s2 subunits; it also generated significantly more trimer complexes between C1r, C1s and C1 inhibitor (C1INH) than did the other two activators. Lipoteichoic acid was, however, a comparatively weak inducer of tetramer C1INH-C1r-C1s-C1INH complexes. Analysis through Western blotting showed that all activators accelerated consumption of C1r, induced complex formations between C1INH and C1s and produced cleavage products of C2. Altogether, the immunochemical analysis gave clear evidence of classical pathway activation by lipoteichoic acid, but its activation profile differed from those seen with lipopolysaccharide and aggregated immunoglobulin G.
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PMID:In vitro activation of the classical pathway of complement by a streptococcal lipoteichoic acid. 800 32

Based on the premise that naturally occurring glycosaminoglycans could serve as building blocks for synthesizing nontoxic drugs for suppression of tumor necrosis factor (TNF) production by inflammatory cells, we have chemically modified hyaluronic acid (HA) and tested its effects in blocking TNF-alpha and TNF-beta production in vitro. HA was chosen mainly for its structural simplicity, nonimmunogenicity, and readiness for chemical modifications. When HA was chemically polysulfated to a sulfate/hexosamine molar ratio of 3.9, the sulfated HAs was shown to be a potent inhibitor of TNF-alpha production in lipopolysaccharide (LPS)- or interferon-gamma-activated THP-1 cells. For example, a concentration of HAs as low as 10 ng/ml reduced TNF-alpha production in LPS-activated THP-1 cells more than 50%, whereas achieving a similar extent of reduction required 50 micrograms/ml native HA. By decreasing the extent of polysulfation, the inhibitory effect of HAs on TNF-alpha production was diminished. Other chemical modifications, including deacetylation, thiolation, or reduction of the carboxylic groups, could not increase the efficacy of HA in suppression of TNF-alpha production. Naturally polysulfated glycosaminoglycans, such as chondroitin sulfates, keratan sulfate, heparan sulfate, and heparin, failed to inhibit TNF-alpha production. HAs also restricted TNF-beta (lymphotoxin) secretion in an Epstein-Barr virus-transformed B cell line, Roha-9, which constitutively produces TNF-beta. HAs had no inhibitory effect on the proliferation of THP-1 or Roha-9 cells, which would account for the reduced TNF-alpha or TNF-beta production. Furthermore, time-course metabolic labeling studies revealed that HAs could not restrict overall protein synthesis and secretion in THP-1 cells. However, HAs increased complement C1q secretion in THP-1 in a dose-dependent manner, but it had no effect on biosynthesis of complement C1 inhibitor, factor D, and Fc gamma receptor type II (Fc gamma RII). These results indicate that HA, selectively restricts the production of TNF-alpha, TNF-beta, and probably several other protein species.
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PMID:Synthetic polysulfated hyaluronic acid is a potent inhibitor for tumor necrosis factor production. 819 3

The subcomponent of complement C1, C1q, mediates complement activation via the classical pathway, and therefore may play an important role in the inflammatory processes in which complement activation is involved. The aim of our study was to investigate C1q synthesis by macrophages of normal and of acutely damaged livers. The localization of C1q in liver tissue was studied by immunohistochemistry. Rat liver tissue macrophages were isolated from normal as well as from acutely damaged (carbon tetrachloride model) liver, and were separated into small, monocyte-like phagocytes and large, mature tissue macrophages, as revealed by immunocytochemistry. C1q gene expression was studied by endogeneous labeling of newly synthesized proteins, immunoprecipitation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and by reverse-transcription polymerase chain reaction (RT-PCR) of C1qB messenger RNA (mRNA). Semiquantitative analysis was performed by Northern blotting of total RNA and hybridization with the radioactively labeled RT-PCR product. C1 esterase inhibitor synthesis was studied in parallel. For comparison, C1q and C1-inhibitor synthesis were also investigated in blood monocytes and peritoneal macrophages. C1q was weakly detectable in sinusoidal cells of the normal liver. C1qB mRNA, as well as constitutive synthesis and secretion of C1q, was clearly detected in freshly isolated and cultured Kupffer cells from normal rat liver. In comparison, newly recruited "inflammatory" macrophages from damaged rat liver synthesized considerably lower amounts of the protein, similar to what was found in the monocyte-like macrophages of normal liver and in peritoneal macrophages. Monocyte C1qB mRNA was not detected even by RT-PCR, and remained undetectable during the time in culture. Similar behavior was observed for C1-inhibitor synthesis. Treatment of the cultures with interferon gamma (IFN-gamma) or lipopolysaccharide (LPS) strongly decreased, whereas treatment with dexamethasone strongly increased C1q gene expression in the macrophage populations, and induced C1qB mRNA in cultured monocytes, as revealed by RT-PCR. Kupffer cells of normal liver may produce considerable amounts of C1q, whereas the inflammatory macrophages of the acutely damaged liver may not be so important for the synthesis of C1q.
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PMID:C1Q synthesis by tissue mononuclear phagocytes from normal and from damaged rat liver: up-regulation by dexamethasone, down-regulation by interferon gamma, and lipopolysaccharide. 921 57

We demonstrate in vitro expression of complement components, i.e. C3, factor H (FH), factor B (FB), C4, C1-inhibitor (C1-inh), C1q, C5, C6, C7 and C9, by four human neuroblastoma cell lines IMR32, SKNSH, SH-SY5Y and KELLY. Activating proteins C4, C9 and C1q, and regulatory proteins FH and C1-inh were produced constitutively by the four cell lines. C3, C6 and FB were mainly produced by SKNSH and SH-SY5Y. Western blot experiments showed that secreted proteins were structurally similar to their serum counterparts. An additional polypeptide of 43 kDa with FH immunoreactivity was detected, which could correspond to the N-terminal truncated form found in plasma. Regulation of complement expression by inflammatory cytokines, lipopolysaccharide and dexamethasone was tested in vitro. These factors had no significant effects on activating synthesis of components C3, FB and C4, but expression of regulating components C1-inh and FH was strongly increased particularly by IFN-gamma and tumor necrosis factor-alpha. The rate of synthesis of complement components was dependent on the differentiation of neuroblastoma cells. This effect of differentiation was also observed on normal rat neurons. Rat cerebellar granule cells constitutively expressed mRNA for C4 and C1q, but expression of C3 mRNA was induced by differentiation. This study shows that neurons could be another local source of complement in the brain, besides astrocytes and microglia. Human neuroblastoma cell lines can constitute an interesting model to analyze complement biosynthesis by human neurons. Local complement expression by neurons in vivo may be implicated in some physio-pathological processes.
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PMID:Expression of a complete and functional complement system by human neuronal cells in vitro. 1088 13

Complement activation is closely associated with plasma endotoxin levels in patients with meningococcal infections. This study assessed complement activation induced by purified Neisseria meningitidis lipopolysaccharide (Nm-LPS), native outer membrane vesicles (nOMVs), LPS-depleted outer membrane vesicles (dOMVs), wild-type meningococci, and an LPS-free mutant (lpxA(-)) from the same strain (44/76) in whole blood anticoagulated with the recombinant hirudin analogue. Complement activation products (C1rs-C1 inhibitor complexes, C4d, C3bBbP, and terminal SC5b-9 complex) were measured by double-antibody EIAs. Nm-LPS was a weak complement activator. Complement activation increased with preparations containing nOMVs, dOMVs, and wild-type bacteria at constant LPS concentrations. With the same protein concentration, complement activation induced by nOMVs, dOMVs, and the LPS-free mutant was equal. The massive complement activation observed in patients with fulminant meningococcal septicemia is, presumably, an indirect effect of the massive endotoxemia. Outer membrane proteins may be more potent complement activators than meningococcal LPSs.
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PMID:Complement activation induced by purified Neisseria meningitidis lipopolysaccharide (LPS), outer membrane vesicles, whole bacteria, and an LPS-free mutant. 1180 96


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