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)

The inflammatory effects of a monocyte-derived neutrophil-activating peptide (MONAP), purified to homogeneity from lipopolysaccharide-stimulated human peripheral blood monocytes, have been evaluated in rabbit skin. Intradermal injection of MONAP alone caused a mild infiltration of polymorphonuclear leucocytes (PMNL) but did not induce any change in plasma extravasation. When combined with prostaglandin E2(PGE2), MONAP caused a marked and synergistic increase in PMNL infiltration and plasma extravasation into the injected skin sites. The increase in vascular permeability induced by MONAP depended on the presence of circulating PMNL. MONAP is a novel cytokine with pro-inflammatory properties and may have physiological and pathophysiological roles in health and disease.
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PMID:Acute inflammatory effects of a monocyte-derived neutrophil-activating peptide in rabbit skin. 266 7

The intrinsic balance of monocyte-derived mediators in the regulation of granulopoiesis was studied. Both the granulocyte macrophage colony-stimulating factors (GM-CSFs) and the colony inhibitory factor (prostaglandin E2; PGE2), were found to be elaborated by cultured monocytes, and most of these mediators were secreted during the first 4 days after monocyte cultivation. The concentration of monocytes in culture had a direct effect on the amount of mediator production. A maximum amount of mediators was noted to range from 2 x 10(5)-2 x 10(6) monocytes per 35 mm Petri dish. It was also found that the monocytes responded to the exogenous stimulus (lipopolysaccharide, LPS) in a biphasic manner. The optimal concentration of LPS in stimulating production of the tested mediators was 3.2 micrograms/ml. At higher concentrations (greater than 3.2 micrograms/ml), both the release of GM-CSFs and PGE2 were suppressed. The addition of indomethacin to the culture system resulted in a confirmatory increase in GM-CSFs production at LPS concentration higher than 3.2 micrograms/ml. The response of monocytes to endogenous regulators (GM-CSFs and PGE2) was also determined. The addition of GM-CSFs to the cultures promoted PGE2 production by monocytes in dose-dependent with an optimal concentration of around 450 units/ml. Alternatively, treatment of monocytes with PGE2 (10(-9) to 10(-10) M) also enhanced, to a certain extent, the production of GM-CSFs. The coincidence of the peaks of GM-CSFs and PGE2 release demonstrated in vitro suggested the existence of an intrinsic balance mechanism in the regulation of granulopoiesis by monocytes.
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PMID:Dual function of monocytes on the regulation of granulopoiesis. 267 31

Macrophages (Mphi) and Mphi-depleted (nonadherent) nonparenchymal cells (NPC) of the liver were examined for their cytotoxic potential against tumor cells, production of tumor necrosis factor (TNF), and release of prostaglandins (PG) following stimulation by lipopolysaccharide (LPS), interferon-gamma (IFN gamma), and zymosan. Resident murine liver macrophages had no natural cytotoxicity for the TNF-resistant target cell line P815. Activation of these cells was only obtained by a combination of IFN gamma and LPS. Inflammatory murine macrophages were in a primed stage and could be activated by LPS alone in the absence of IFN gamma. Rat resident macrophages resembled functionally the inflammatory macrophages of the mouse liver rather than the resident macrophages. They displayed natural cytotoxicity against all targets tested and were further activated by LPS in the absence of IFN gamma. Similar results were obtained with respect to macrophage-depleted nonadherent NPC: Mouse NPC had a low level of NK activity against Yac-1 cells. Treatment with pyran copolymer resulted in a strong increase of cytotoxicity against Yac-1; furthermore, a TNF-dependent killing of Wehi 164 and TNF-independent cytotoxicity against P815 cells were now acquired. In the rat NPC prepared from unstimulated animals expressed high levels of natural cytotoxicity against all targets. No major differences could be observed between inflammatory Mphi and Kupffer cells of rat and mouse liver with regard to TNF production and TNF-dependent killing of Wehi 164 tumor cells. The same was true for the spectrum of secreted prostanoids. Upon activation of all cell populations a marked shift toward the production of PGE2 occurred. Experiments involving the cyclooxygenase inhibitor indomethacin showed enhanced TNF-dependent tumor cell killing by nonactivated Mphi in the absence of prostanoid production.
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PMID:Comparative study of cytotoxicity, tumor necrosis factor, and prostaglandin release after stimulation of rat Kupffer cells, murine Kupffer cells, and murine inflammatory liver macrophages. 278 25

These studies utilized a sensitive and specific radioimmunoassay for interleukin 1 beta (IL-1 beta) to compare release of IL-1 by human alveolar macrophages and blood monocytes. The studies demonstrate that alveolar macrophages release amounts of antigenic IL-1 beta that are similar to that of blood monocytes. The amounts of IL-1 released were similar for both cell types at early (4 h) and late (24 h) time points and with differing amounts of stimuli [endotoxin; lipopolysaccharide (LPS)]. In addition, alveolar macrophages actually produced more total IL-1 (intracellular IL-1 plus released IL-1) than did blood monocytes. Alveolar macrophages that were stimulated with LPS released significantly more prostaglandin E2 (PGE2, an inhibitor of IL-1) than did blood monocytes. These studies demonstrate that human alveolar macrophages are not defective in their capacity to release IL-1.
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PMID:Interleukin 1 release by human alveolar macrophages and blood monocytes. 278 63

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.
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PMID:Up- and down-regulation of human lymphokine (IL-2)-activated killer cell induction by monocytes, depending on their functional state. 282 45

In the preceding paper it was shown that Kupffer cells isolated by digestion of the liver and purified by centrifugal elutriation can be activated in vitro by lipopolysaccharide and muramyl dipeptide to an enhanced superoxide response upon zymosan phagocytosis. Lipopolysaccharide and muramyl dipeptide also led to a strongly increased prostaglandin E2 release during the phagocytosis of zymosan. This activation was accompanied by an increased production of prostaglandin E2 during the incubation with the stimuli. Prostaglandin E2 synthesis was inhibited by the cyclooxygenase inhibitor indomethacin, reduced by dexamethasone, but only slightly decreased by the lipoxygenase inhibitor nordihydroguaiaretic acid. Indomethacin and dexamethasone also reduced the superoxide response, which only in the case of indomethacin is reversed by exogenous prostaglandin E2. Dexamethasone reduced the superoxide response in unstimulated cells as well. From these results it is deduced that cyclo-oxygenase products, especially prostaglandin E2, but not lipoxygenase products, i.e. leukotrienes, play some regulatory role in the activation process of Kupffer cells; in addition, a prostaglandin-independent inhibition exerted by dexamethasone seems to exist.
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PMID:Guinea pig Kupffer cells can be activated in vitro to an enhanced superoxide response. II. Involvement of eicosanoids. 285 91

The inhibition of prostaglandin generation by AD-1590 was investigated in the rabbit brain in-vivo. AD-1590 (0.4 mg kg-1 i.v.) markedly prevented both the increases in body temperature and PGE2 level in cerebrospinal fluid (CSF) caused by i.v. injection of lipopolysaccharide. On the other hand, 2,4-dinitrophenol (20 mg kg-1 i.v.)-induced hyperthermia, which was not affected by AD-1590, was not accompanied by an increase in PGE2 level in CSF. When injected intracerebroventricularly, AD-1590 dose-dependently inhibited the hyperthermia caused by arachidonic acid given by the same route; its ED50 was 1.6 micrograms compared with about 35 micrograms for indomethacin. From these results, it is suggested that AD-1590 is more active than indomethacin in suppressing prostaglandin synthetase in rabbit brain.
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PMID:Inhibition of prostaglandin generation in the rabbit brain in-vivo by AD-1590, a non-steroidal anti-inflammatory agent with potent antipyretic activity. 286 98

Dexamethasone inhibited the stimulus-induced prostaglandin E2 formation by rat Kupffer cells in primary culture, e.g. after treatment with zymosan, phorbol ester, calcium ionophore A23187, platelet-activating factor or lipopolysaccharide. Prostaglandin E2 production from added free arachidonic acid was not influenced by the hormone. The time course, as well as the partial inhibition of the hormone effect by actinomycin D and cycloheximide, point to the hormone-induced formation of a protein which regulates phospholipase A2. The hormone did not affect the phagocytotic activity of the Kupffer cells. The quantity of [3H]arachidonic acid incorporated into phospholipids was also not altered by dexamethasone. After stimulation with zymosan, [3H]arachidonic acid was liberated from phosphatidylcholine only. Superoxide generation by rat Kupffer cells was induced by zymosan, phorbol ester and, to a much smaller extent, by platelet-activating factor. A23187 and lipopolysaccharide were without effect. In contrast to prostaglandin formation, the generation of superoxide was not influenced by dexamethasone. These results indicate that in cultured rat Kupffer cells prostaglandin formation and superoxide generation are independently triggered processes.
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PMID:Differential inhibition of prostaglandin and superoxide production by dexamethasone in primary cultures of rat Kupffer cells. 301 94

Macrophages, which produce the collagenolytic enzyme collagenase, are commonly found at sites of connective tissue destruction in chronic inflammatory lesions. Since tissue macrophages are derived from circulating peripheral blood monocytes, we used these less-differentiated, more readily available cells to examine the production and regulation of collagenase. Human monocytes, isolated in large quantities by counterflow centrifugal elutriation, were shown to produce substantial amounts of collagenase when stimulated by concanavalin A (Con A) and to a lesser extent with lipopolysaccharide, while unstimulated monocyte cultures produced negligible collagenase. Collagenase was detected in the culture media within the first 24 hr of culture after activation with peak production at 48 hr. Analysis of the intracellular regulation of collagenase revealed that synthesis of this enzyme required a prostaglandin (PGE2)-dependent step since indomethacin-inhibited enzyme synthesis was reversed by PGE2. Additionally, dibutyryladenosine cyclic monophosphate (dBcAMP) restored collagenase synthesis in indomethacin-blocked cultures, indicating a PGE2-dependent generation of cAMP requirement for collagenase production similar to that demonstrated in experimental animals systems. In additional studies, anti-inflammatory drugs which are known to modulate connective tissue destruction were analyzed for their influence on monocyte-derived collagenase. Dexamethasone, colchicine or retinoic acid all inhibited collagenase synthesis by monocytes in a dose-dependent manner although the effect of these drugs on monocyte PGE2 synthesis differed. Dexamethasone inhibited PGE2 synthesis, which resulted in the suppression of collagenase. However, PGE2 production was unaffected by colchicine whereas retinoic acid caused a significant increase in PGE2 levels. Inhibition of collagenase synthesis by dexamethasone, but not colchicine or retinoic acid, could be reversed by PGE2 or phospholipase A2. These findings provide insight into the intracellular events regulating monocyte collagenase synthesis and also implicate monocytes as a target of anti-inflammatory agents which ameliorate connective tissue degradation associated with chronic inflammatory lesions.
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PMID:Regulation of human peripheral blood monocyte collagenase by prostaglandins and anti-inflammatory drugs. 303 63

Preexposure of resident mouse peritoneal macrophages for 1 hr to traces of bacterial lipopolysaccharide (LPS) (less than or equal to 1 ng/ml) rendered the cells refractory to activation by recombinant interferon-gamma (rIFN gamma) or recombinant tumor necrosis factor-alpha (rTNF alpha), as evaluated by release of H2O2 upon stimulation with phorbol myristate acetate. Inhibition persisted for at least 4 days. Fifty percent inhibition of activation mediated by rIFN gamma followed 1 hr exposure to 10 pg/ml LPS. Fifty percent inhibition of activation mediated by rTNF alpha was achieved with 1 hr exposure to 1 pg/ml LPS. Such low levels LPS exposures (concentration X time) are far below those reported for many other actions of LPS on host cells. Inhibition was partially prevented by the cyclooxygenase inhibitors indomethacin, ibuprofen, and acetylsalicylic acid. Exogenous prostaglandins PGE1 and PGE2, and the 3',5'-cyclic adenosine monophosphate analog dibutyryl cyclic adenosine monophosphate (cAMP), mimicked the inhibitory effect of LPS in a dose-dependent manner, consistent with the hypothesis that formation of endogenous cyclooxygenase products in response to LPS may elevate intracellular cAMP and that the latter may mediate the observed inhibition. In addition, neutralizing antibody against IFN alpha and IFN beta selectively prevented LPS inhibition of activation mediated by rIFN gamma, but not by rTNF alpha. This suggests that IFN alpha and/or IFN beta induced by LPS also contributed to inhibition of activation by rIFN gamma. Thus, release of LPS may afford microorganisms a means by which to interfere with immunologically mediated enhancement of the respiratory burst-dependent antimicrobial capacity of macrophages.
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PMID:Trace levels of bacterial lipopolysaccharide prevent interferon-gamma or tumor necrosis factor-alpha from enhancing mouse peritoneal macrophage respiratory burst capacity. 304 Aug 60


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