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)

A Limulus intracellular coagulation inhibitor, designated LICI, was isolated from hemocytes of the Japanese horseshoe crab (Tachypleus tridentatus), using three steps of chromatography, including dextran sulfate-Sepharose CL-6B, Sephacryl S-200, and Mono S. LICI is a single-chain glycoprotein with an apparent M(r) = 48,000 estimated by SDS-polyacrylamide gel electrophoresis. It blocks the amidolytic activities of Limulus lipopolysaccharide-sensitive serine protease, factor C, by forming a covalent 1:1 complex with the protease. The second-order rate constant for inhibition of factor C was 2.5 x 10(6) M-1 s-1 at 37 degrees C. LICI also inhibited human alpha-thrombin, rat salivary kallikrein, bovine plasmin, and trypsin but not Limulus clotting enzyme, Limulus factor B, bovine factor Xa, human factor XIa, human tissue plasminogen activator, human urokinase, chymotrypsin, elastase, and papain. Glycosaminoglycans such as heparin and heparan sulfate had no effect on the inhibitory activity. A cDNA coding for LICI was isolated from a hemocyte cDNA library. The open reading frame of the 1,257-base pair cDNA codes for the mature protein of 394 amino acids, of which 223 residues were confirmed by amino acid sequence analysis. LICI shows significant sequence identities to members of the serpin superfamily, such as human plasminogen activator inhibitor type 2 (40%) and human monocyte/neutrophil elastase inhibitor (39%). LICI contains a putative reactive site, -Arg-Ser-, at the corresponding position present in several inhibitors of the serpin superfamily. The subcellular localization, determined using an anti-LICI polyclonal antibody, indicated that LICI colocates with the Limulus serine protease zymogens in large granules in the hemocyte.
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PMID:A Limulus intracellular coagulation inhibitor with characteristics of the serpin superfamily. Purification, characterization, and cDNA cloning. 827 48

epsilon receptor modulating protein (epsilon RMP) was identified and purified in our previous studies as a murine T cell-derived soluble 17-kDa chymotryptic serine protease which suppresses avidity of binding between IgE and CD23 (low affinity Fc receptor for IgE) without decreasing the quantitative expression of the CD23 molecule. Some, but not all, of the other known soluble serine proteases showed epsilon RMP-like CD23-modulating activities. Further studies indicated that epsilon RMP exists not only as a soluble protein but also as a 36-kDa T-cell surface form. Both soluble and membrane-bound epsilon RMP can induce purified splenic B cells to secrete IgE in the presence of IL-4 even without lipopolysaccharide (LPS). In this study, therefore, we have tested effects of several known serine proteases on Ig production in vitro and have found that: (i) coculture of splenic B cells in the presence of LPS and IL-4 with serine proteases which have epsilon RMP-like substrate specificity, such as kallikrein and alpha-chymotrypsin, results in a significant increase of IgG1 and a slight increase of IgE secretion at low concentrations, and significant suppression at high concentrations in an isotype-selective manner; and (ii) the effects of these proteases are blocked by phenylmethylsulfonyl fluoride but not by indomethacin, suggesting that serine protease activity but not prostaglandin E2 is involved. The biological significance of the possible involvement of serine proteases on Ig class switching is discussed.
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PMID:Biphasic effect of kallikrein on IgE and IgG1 syntheses by LPS/IL-4-stimulated B cells. 842 28

Our biochemical studies on the hemolymph coagulation-complement system using limulus indicate that the circulating hemocytes contain at least four serine protease zymogens and one clottable protein, coagulogen, which constitute a cascade triggered by bacterial endotoxins and (1,3)-beta-D-glucan. We also found several antimicrobial substances, tachyplesin peptides and anti-lipopolysaccharide factor, in the hemocytes. These clotting factors and antimicrobial substances are released into the hemolymph in response to lipopolysaccharide, where they cooperate in immobilization and killing of invading microorganisms as a host defense.
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PMID:The limulus clotting reaction. 845 77

We investigated the effect of activated protein C (APC) on lipopolysaccharide (LPS)-induced pulmonary vascular injury in rats to investigate the possible usefulness of APC as a treatment for adult respiratory distress syndrome. Intravenously administered LPS (5 mg/kg) significantly increased pulmonary vascular permeability. APC prevented the LPS-induced increase in pulmonary vascular permeability observed at 6 hours. Heparin plus antithrombin III (ATIII) and active site-blocked factor Xa (DEGR-Xa), a selective inhibitor of thrombin generation, inhibited LPS-induced coagulopathy but did not prevent LPS-induced pulmonary vascular injury. LPS-induced pulmonary vascular injury was significantly attenuated in rats with nitrogen mustard-induced leukocytopenia and in rats treated with ONO-5046, a potent granulocyte elastase inhibitor. Administration of LPS also increased pulmonary accumulation of leukocytes, as evaluated by measurement of myeloperoxidase activity in the lungs. APC significantly reduced LPS-induced increases in pulmonary accumulation of leukocytes at 1 hour. Neither ATIII plus heparin nor DEGR-Xa inhibited leukocyte accumulation. Active site-blocked APC (DIP-APC) prevented neither the LPS-induced pulmonary accumulation of leukocytes nor the LPS-induced increase in pulmonary vascular permeability. These results suggest that the mechanism of APC inhibition of LPS-induced pulmonary vascular injury was independent of its anticoagulant activity and was related to its ability to inhibit accumulation of leukocytes. In addition, these findings suggest that the serine protease activity of APC may be essential to its inhibitory effect on LPS-induced pulmonary accumulation of leukocytes and subsequent pulmonary vascular injury.
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PMID:Activated protein C attenuates endotoxin-induced pulmonary vascular injury by inhibiting activated leukocytes in rats. 855 86

Monocytes freshly isolated from human blood produced large amounts of superoxide when triggered by phorbol ester. After monocytes were cultured for 18-24 hr in endotoxin-free, non-adherent conditions, they produced low amounts of superoxide. Addition of lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), or platelet-activating factor (PAF) at the beginning of culture 'primed' the monocytes, causing them to maintain a high superoxide response for at least 96 hr. Also, in response to LPS, monocytes secreted TNF-alpha. The ability of LPS, IFN-gamma, TNF-alpha or PAF to maintain the high superoxide response was blocked by addition of inhibitors of serine proteases, either 4-(2-aminoethyl)-benzenesulphonyl fluoride (AEBSF) or 3,4-dichloroisocoumarin. AEBSF was most effective at 200 microns, and required 6 hr for maximum effect. AEBSF did not affect phorbol-triggered superoxide release by unprimed monocytes. AEBSF did not affect cell viability, nor did it interfere with the TNF-alpha secretion in response to LPS. An analogue of AEBSF that lacked ability to inhibit proteases did not affect monocyte responses. 3,4-Dichloroisocoumarin blocked priming at a low concentration, 1 microM. We conclude that activity of a monocyte serine protease is required to maintain the high superoxide response in monocytes primed with LPS, IFN-gamma, TNF-alpha, or PAF.
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PMID:Serine protease inhibitors block priming of monocytes for enhanced release of superoxide. 856 31

We report here the isolation and characterization of a new member of the ice/ced-3 family of cell death genes, named ich-3. The predicted amino acid sequence of Ich-3 protein shares 54% identity with murine interleukin-1beta converting enzyme (ICE). Overexpression of ich-3 in Rat-1 and HeLa cells induces apoptosis, which can be inhibited by CrmA and Bcl-2. The mRNA and proteins of ich-3 are dramatically induced in vivo upon stimulation with lipopolysaccharide, an inducer of septic shock. The ich-3 gene product can be cleaved by cytotoxic T cells granule serine protease granzyme B, suggesting that Ich-3 may mediate apoptosis induced by granzyme B. Ich-3 does not process proIL-1beta directly but does promote proIL-1beta processing by ICE. These results suggest that Ich-3 may play a very important role in apoptosis and inflammatory responses and may be an upstream regulator of ICE.
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PMID:Identification and characterization of Ich-3, a member of the interleukin-1beta converting enzyme (ICE)/Ced-3 family and an upstream regulator of ICE. 870 3

Invertebrate animals, which lack adaptive immune systems, have developed defense systems that respond to common antigens on the surface of potential pathogens. Hemolymph coagulation is one such defense system in innate immunity. The discovery of lipopolysaccharide-sensitive and (1-->3)-beta-D-glucan-sensitive serine protease zymogens in horseshoe crab (limulus) hemocytes, both of which trigger the coagulation cascade, has exemplified how the animals detect and respond to foreign materials.
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PMID:The role of hemolymph coagulation in innate immunity. 872 45

Most bacterial and fungal proteases excreted into infected hosts exhibit a wide range of pathogenic potentials ranging from pain, edema or even shock to translocation of bacteria from the site of infection into systemic circulation, thus resulting in septicemia. The basic mechanism or principle common to all these phenomena is explained by kinin generation, either directly from high- and/or low-molecular weight kininogens or indirectly via activation of the bradykinin generating cascade: i.e. Hageman factor-->activated Hageman factor-->prekallikrein-->kallikrein-->high-molecular weight kininogen-->bradykinin. Some bacterial proteases are also involved in activation of other host protease zymogens such as plasminogen, procollagenase (matrix metallo proteases) and proenzymes of the clotting system. Furthermore, most bacterial proteases are not only resistant to plasma protease inhibitors of the hosts, most of which belong to a group of serine protease inhibitors called serpins (serine protease inhibitors), but they also quickly inactivate serpins. Some bacterial proteases may also activate bacterial toxins thus rendering toxigenic pathogenesis. They are also capable of degrading immunoglobulins and components of the complement system and facilitate propagation of micro organisms. All in all, microbial proteases are very critical in enhancing pathogenesis of severe diseases. It is also noteworthy that bacterial cell wall components themselves, i.e. endotoxin (or lipopolysaccharide) of gram negative bacteria and teichoic/lipoteichoic acid of gram positive bacteria, are also able to activate the bradykinin generating cascade-involving activation of Hageman factor as mentioned above.
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PMID:Pathogenic mechanisms induced by microbial proteases in microbial infections. 873 87

We reported that limulus intracellular coagulation inhibitor type-1 (LICI-1) (Miura, Y., Kawabata, S., and Iwanaga, S. (1994) J. Biol. Chem. 269, 542-547) and LICI type-2 (LICI-2) (Miura, Y., Kawabata, S. , Wakamiya, Y., Nakamura, T., and Iwanaga, S. (1995) J. Biol. Chem. 270, 558-565) found in the hemocyte lysate belong to the serpin family. The LICI-1 specifically inhibits limulus lipopolysaccharide-sensitive serine protease, factor C (k1 = 2.5 x 10(6) M-1 s-1), whereas LICI-2 inhibits preferentially limulus clotting enzyme (k1 = 4.3 x 10(5) M-1 s-1). In our ongoing studies on limulus serpin, we found another inhibitor, named LICI type-3 (LICI-3), which strongly inhibits (1,3)-beta-D-glucan-sensitive serine protease, factor G (k1 = 3.9 x 10(5) M-1 s-1). Thus, the limulus hemolymph coagulation cascade is effectively regulated by at least the three endogenous serpins. LICI-3, newly identified in hemocytes, is a single chain glycoprotein with an apparent Mr = 53,000, the largest one among known limulus serpins. A cDNA sequence for LICI-3 coded a mature protein of 392 amino acids, of which 68 residues were confirmed by peptide sequencing. LICI-3 showed significant sequence similarity to LICI-1 (45.8% identity) and LICI-2 (33.7% identity). LICI-3 contained a putative reactive site, -Arg-Ser-, distinct from that of LICI-2 (-Lys-Ser-) but the same as that of LICI-1. Expression of LICI-3 mRNA was detected only in hemocytes, and not in heart, brain, stomach, intestine, coxal gland, and skeletal muscle. Immunoblotting of the hemocyte-derived large and small granules with antiserum against LICI-3 suggested that it is stored specifically in large granules, as in the case of LICI-1 and LICI-2, and is released in response to external stimuli.
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PMID:Limulus intracellular coagulation inhibitor type 3. Purification, characterization, cDNA cloning, and tissue localization. 879 3

In this review, we present arguments indicating that prophenoloxidase (proPO) activating system acts as a pattern recognition and defence system in invertebrate blood. Phenoloxidase (PO) activity has been found in the blood of many invertebrates. At least in arthropods, echinoderms and urochordates, the inactive pro-form, proPO has been found to be elicited by the microbial cell-wall components beta-1, 3-glucans, lipopolysaccharide and/or peptidoglycan. This activation seems to involve elicitor-binding proteins and serine protease(s). ProPO, the proPO-activating enzyme (ppA) and plasma elicitor-binding proteins, have been purified from some arthropods, and proPO and the beta-1, 3-glucan binding protein (beta GBP) have been cloned and sequenced from crayfish. Arthropod proPO has a molecular mass of 70-90 kDa and PO has a molecular mass of 60-70 kDa. The beta GBP also stimulates phagocytosis of fungal cells and, after reacting with beta-1, 3-glucan, blood-cell degranulation (and release of the proPO system). In addition, a cell-adhesion protein (of 70-100 kDa), apparently associated with the proPO system, has been purified from arthropods. This mediates blood-cell adhesion, degranulation, phagocytosis and encapsulation. The cell-adhesion protein and beta GBP bind to a common blood-cell membrane receptor. It would be interesting to see the sequences of more proPO system components and investigate whether the scheme for cellular communication and defence, involving the cell-adhesion protein, elicitor-binding proteins and the membrane receptor described in arthropods, applies to invertebrates in general.
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PMID:The prophenoloxidase activating system and associated proteins in invertebrates. 896 65


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