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 emigration of leukocytes across the blood-endothelium barrier and their subsequent transmigration through the interstitium is a complex process that is vital for maintaining the efficiency of the body's innate and adaptive immunity. The chemokines, a family of low-molecular-weight chemoattractant cytokines, are well recognized to be key players in this process. However, recent investigations have highlighted an important role played by the selectin family of adhesion molecules in enhancing chemokine functions. This review summarizes the in vitro and in vivo studies that support this growing notion. It discusses chemotaxis in the context of the phosphoinositide 3-kinase and p38 mitogen-activated protein kinase pathways, and their relation to several chemoattractants (i.e., interleukin-8, leukotriene-B(4), formyl-methionyl-leucyl-phenylalanine, keratinocyte-derived cytokine, and macrophage inflammatory protein-2), the possible role played by L-selectin, and finally how chemotaxis can be altered in different inflammatory settings, such as lipopolysaccharide-mediated endotoxemia or chronic vasculitis.
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PMID:L-selectin: an emerging player in chemokine function. 1285 51

Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis that is associated with systemic inflammation. The aim of our study was to assess whether plasma markers of inflammation increased after exercise in patients with PAD. The study was conducted on two groups of 20 subjects each: one group (mean age 68.4 +/- 5.09 years) was affected by PAD with claudication, while the other group consisted of healthy controls (66.9 +/- 6.1 years). Concentrations of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFalpha) were determined in plasma, in supernatants and in cells stimulated with 1 mg lipopolysaccharide in all patients. E-selectin (ES), L-selectin (LS) and P-selectin (PS) concentrations and plasma concentrations of VCAM-1 and ICAM-1 were also determined. All determinations were performed in patients at rest and after the treadmill exercise. Resting values of soluble mediators were greater in PAD patients than in controls. They increased in both groups after the treadmill test, even if post-treadmill concentrations were significantly higher in PAD patients (PAD p < 0.001 or 0.0001, controls p < 0.05 or 0.001). These results confirm that white blood cell activation is characteristic of systemic atherosclerosis and that these inflammation markers increase in conditions of hemodynamic stress.
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PMID:High circulating levels of cytokines (IL-6 and TNFalpha), adhesion molecules (VCAM-1 and ICAM-1) and selectins in patients with peripheral arterial disease at rest and after a treadmill test. 1286 7

The aim of this in vivo study was to examine the effect of intramammarily administered endotoxin (lipopolysaccharide, LPS) on the expression of L-selectin (CD62L) and the beta2-integrin subunits CD11b and CD18 on circulating bovine PMN. Six early lactating cows were infused with Escherichia coli LPS. The adhesion molecules under study were stained at the cell surface and analyzed flow cytometrically. In addition, some of the clinical parameters associated with adhesion molecule mobilization such as fever, blood cortisol levels, somatic cell count (SCC), and total and differential blood leukocyte count were measured. In analogy with observations during clinical coliform mastitis, a progressive decrease of CD62L expression levels was observed early after LPS infusion, concomitantly with a continuous rise of CD11b and CD18 density. However, no correlation was found between the kinetics of CD11b and CD18 density. The initial changes in adhesion molecule expression paralleled the decrease in blood PMN numbers, together with the increase in rectal temperature, cortisol levels, SCC, and number of circulating immature PMN. In conclusion, intramammarily administered LPS seems to play an important role in modulating adhesion receptor expression on circulating bovine PMN. Interestingly, in contrast to coliform mastitis, the net CD18 variation is not principally influenced by CD11b upregulation during endotoxin administration. The knowledge of adhesion molecule kinetics in relation to the different parameters evaluated in the present study contributes to an improved understanding of the inflammatory reaction.
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PMID:L-selectin and beta2-integrin expression on circulating bovine polymorphonuclear leukocytes during endotoxin mastitis. 1290 50

Paradoxically, the host response to severe sepsis may lead to immunosuppression, thereby favoring nosocomial infections. We examined the role of the two IL-12 isoforms, bioactive IL-12p70 and regulatory IL-12p40, in 16 patients with severe sepsis. We compared the capacity of purified blood and alveolar phagocytes [polymorphonuclear neutrophils (PMN) and monocytes/macrophages] to secrete each isoform. Blood monocytes had normal basal secretions. In contrast, a marked imbalance was observed after ex vivo stimulation by lipopolysaccharide plus IFN-gamma, with significantly lower IL-12p70 production and higher IL-12p40 production. Conversely, stimulated IL-12p40 production by the patients' blood PMN tended to be impaired, as was their cell-surface beta2 integrin and L-selectin expression, known as markers of cell activation. In the patient's bronchoalveolar lavage fluid, the production of both IL-12 isoforms after ex vivo stimulation was significantly lower with alveolar macrophages than with autologous blood monocytes and significantly higher with alveolar PMN than with autologous blood PMN. This sheds new light on the potential role of PMN in local modulation of inflammation, via secretion of the anti-inflammatory IL-12 p40 subunit. The imbalance between the bioactive and regulatory IL-12 isoforms, which is probably designed to control excessive inflammation, may also make septic patients more susceptible to nosocomial infection.
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PMID:Regulation of interleukin 12 p40 and p70 production by blood and alveolar phagocytes during severe sepsis. 1367 43

Leukocyte recruitment in the liver includes a two-step procedure in which selectin-dependent leukocyte rolling is a prerequisite for subsequent CD18-dependent leukocyte firm adhesion in postsinusoidal venules. However, the roles of the individual selectins in leukocyte rolling and adhesion, hepatocellular injury, and apoptosis remain elusive. Therefore, we examined the pathophysiological role of P-, E-, and L-selectin in male C57BL/6 mice challenged with lipopolysaccharide (LPS) and D-galactosamine (Gal) by use of intravital microscopy of the liver microcirculation. In control animals, administration of LPS-Gal provoked reproducible hepatic damage, including marked increases of leukocyte recruitment, liver enzymes, and hepatocyte apoptosis and reduced sinusoidal perfusion. Interestingly, pretreatment with an anti-P-selectin antibody (RB40.34) markedly reduced leukocyte rolling and firm adhesion by 65 and 71%, respectively. Moreover, interference with P-selectin function significantly improved sinusoidal perfusion and reduced the increase in liver enzymes by 49 to 84% in endotoxemic mice. Moreover, the activity of caspase-3 and the number of apoptotic hepatocytes were significantly reduced by 55 and 54%, respectively, in RB40.34-treated animals. In contrast, administration of an anti-E-selectin antibody (10E9.6) and an anti-L-selectin antibody (Mel-14) did not protect against endotoxin-induced leukocyte responses or hepatic injury. In conclusion, our novel findings document a principal role of P-selectin in mediating leukocyte rolling, a precondition to the subsequent firm adhesion of leukocytes in liver injury. Furthermore, our novel data demonstrate that inhibition of P-selectin function reduces hepatocellular injury and apoptosis, suggesting a causal relationship between leukocyte recruitment on one hand and hepatocellular injury and apoptosis on the other hand. Based on these findings, it is suggested that P-selectin may be an important therapeutic target in endotoxin-induced liver injury.
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PMID:Important role of P-selectin for leukocyte recruitment, hepatocellular injury, and apoptosis in endotoxemic mice. 1471 45

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of morbidity and mortality in the intensive care unit, but despite continuing research few effective therapies have been identified. In recent years, inhaled carbon monoxide (CO) has been reported to have cytoprotective effects in several animal models of tissue injury. We therefore evaluated the effects of inhaled CO in three different in vivo mouse models of ALI. Anesthetized C57BL/6 mice were ventilated with oxygen in the presence or absence of CO (500 parts per million) for 1 h before lung injury was induced by lipopolysaccharide (LPS) or oleic acid (OA) administration. Ventilation was then continued with the same gases for a further 2-3 h, with hemodynamic and respiratory parameters monitored throughout. Intratracheal LPS administration induced lung injury with alveolar inflammation (increased lavage fluid neutrophils, total protein, and cytokines). In contrast, intravenous LPS induced a predominantly vascular lung injury, with increased plasma TNF and increased neutrophil activation (surface Mac-1 upregulation and L-selectin shedding) and sequestration within the pulmonary vasculature. Intravenous OA produced deteriorations in lung function, reflected by changes in respiratory mechanics and blood gases and lavage fluid neutrophil accumulation. However, addition of CO to the inspired gas did not produce significant changes in the measured physiological or immunological parameters in the mouse models used in this study. Thus the results do not support the hypothesis that use of inhaled CO is beneficial in the treatment of ALI and ARDS.
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PMID:Effects of inhaled carbon monoxide on acute lung injury in mice. 1568 91

Ehrlichia chaffeensis, an obligately intracellular bacterium, resides within a cytoplasmic vacuole in macrophages, establishes persistent infection in natural hosts such as white-tailed deer and canids, and is transmitted transstadially and during feeding by ticks, particularly Amblyomma americanum. Ehrlichial cell walls contain glycoproteins and a family of divergent 28 kDa proteins, but no peptidoglycan or lipopolysaccharide. The dense-cored ultrastructural form preferentially expresses certain glycoproteins, including a multiple repeat unit-containing adhesin. Ehrlichiae attach to L-selectin and E-selectin, inhibit phagolysosomal fusion, apoptosis, and JAK/STAT activation, and downregulate IL-12, IL-15, IL-18, TLR2 and 3, and CD14. Mouse models implicate overproduction of TNF-alpha by antigen-specific CD8 T lymphocytes in pathogenesis and strong type 1 CD4 and CD8 T lymphocyte responses, synergistic activities of IFN-gamma and TNF-alpha, and IgG2a antibodies in immunity. Human monocytotropic ehrlichiosis (HME) manifests as a flu-like illness that progresses in severity to resemble toxic shock-like syndrome, with meningoencephalitis or adult respiratory distress syndrome in some patients, and requires hospitalization in half. In immunocompromised patients, HME acts as an overwhelming opportunistic infection. In one family physician's practice, active surveillance for three years revealed an incidence of 1000 cases per million population. Diagnosis employs serology or polymerase chain reaction, which are not utilized sufficiently to establish the true impact of this emerging virus-like illness.
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PMID:Ehrlichia under our noses and no one notices. 1635 25

We evaluated the effects of magnetic resonance (MR) imaging on human neutrophil functions. In addition of the counting of leukocyte and neutrophil number, expression levels of adhesion molecules on neutrophil surface such as CD11b and L-selectin, and reactive oxygen species (ROS) production were determined by means of flowcytometry. Complete blood count did not show any difference between before and after MR imaging in five normal healthy volunteers. The levels of cell surface adhesion molecules were not altered in both in vivo MR imaging (n=5) and in vitro MR exposure experiments (n=13). Moreover, the levels of ROS production were also not affected by in vivo MR imaging. On the other hand, neutrophils exposed to MR in vitro exhibited significant increase in ROS production after stimulation with fMLP combined with lipopolysaccharide, although no increase was observed with PMA stimulation. Actually, there have been no reports describing the complication relating to hyper-neutrophil function as far as we could search, but it might be necessary to evaluate the biological effects of MR imaging especially under the pathologic circumstances that induce neutrophil activation.
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PMID:[Effects of magnetic resonance imaging on neutrophil functions]. 1678 15

Heparin is an excellent inhibitor of P- and L-selectin binding to the carbohydrate determinant, sialyl Lewis(x). As a consequence of its anti-selectin activity, heparin attenuates metastasis and inflammation. Here we show that fucosylated chondroitin sulfate (FucCS), a polysaccharide isolated from sea cucumber composed of a chondroitin sulfate backbone substituted at the 3-position of the beta-D-glucuronic acid residues with 2,4-disulfated alpha-L-fucopyranosyl branches, is a potent inhibitor of P- and L-selectin binding to immobilized sialyl Lewis(x) and LS180 carcinoma cell attachment to immobilized P- and L-selectins. Inhibition occurs in a concentration-dependent manner. Furthermore, FucCS was 4-8-fold more potent than heparin in the inhibition of the P- and L-selectin-sialyl Lewis(x) interactions. No inhibition of E-selectin was observed. FucCS also inhibited lung colonization by adenocarcinoma MC-38 cells in an experimental metastasis model in mice, as well as neutrophil recruitment in two models of inflammation (thioglycollate-induced peritonitis and lipopolysaccharide-induced lung inflammation). Inhibition occurred at a dose that produces no significant change in plasma activated partial thromboplastin time. Removal of the sulfated fucose branches on the FucCS abolished the inhibitory effect in vitro and in vivo. Overall, the results suggest that invertebrate FucCS may be a potential alternative to heparin for blocking metastasis and inflammatory reactions without the undesirable side effects of anticoagulant heparin.
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PMID:Selectin blocking activity of a fucosylated chondroitin sulfate glycosaminoglycan from sea cucumber. Effect on tumor metastasis and neutrophil recruitment. 1737 80

The adhesion of the monocytes to the endothelium and their extravasation into the intima are key steps in atherogenesis. Studies showed the essential role of L-selectin (CD62-L), expressed by the monocytes, and the platelets by forming complexes with monocytes. The delipided apolipoprotein (Apo) A or high-density lipoprotein (HDL) has antiinflammatory effects on monocytes and can bind platelets (monocyte-platelet complexes [MPCs]). The aim of this study was to identify a possible relationship between the MPCs, the monocyte subset, and ApoA-I/HDL serum levels in vivo. Platelet-monocyte complexes were estimated by flow cytometry in 16 volunteers. Monocyte-platelet interaction was characterized by the percentage of monocytes coexpressing the constitutive platelet marker, glycocalicin gpIb-alpha (CD42b; CD42b+monocytes in %, MPC%). Monocytes were divided into four subsets based on lipopolysaccharide receptor (CD14) and FcgammaIII receptor (CD16) expression (CD14++/CD16-, G1; CD14++/CD16+, G2; CD14+/CD16-, G3; and CD14+/CD16+, G4). HDL and ApoA-I levels were measured by routine laboratory techniques. MPC% in the different subsets were G1=8.1+/-3.4%, G2=21.2+/-14%, G3=18+/-12.6%, and G4=22.3+/-14.3% (analysis of variance: P<.001). MPC% in the entire monocyte population was negatively correlated to ApoA-I (R=-0.71, P=.001). The relationship between ApoA-I and MPC% was found mainly in the subsets G1 (R=-0.67, P=.001) and G2 (R=-0.61, P=.01). MPC% was not correlated with any other lipids or lipoprotein or high-sensitivity C-reactive protein. When whole blood was incubated with HDL/ApoA-I, no modification of platelet CD42b fluorescence was observed, indicating that there is no direct interaction between the HDL/ApoA-I and the CD42b fluorescence. Among the monocytes, the G2 subset appeared to have the highest extravasation potential. Indeed, we previously showed that those cells overexpressed CD62-L, and we observed in this work that they were coated with platelets more than the G1 cells. The G2 subset could be more directly involved in the development of atherosclerotic lesions.
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PMID:Monocyte-platelet complexes on CD14/CD16 monocyte subsets: relationship with ApoA-I levels. A preliminary study. 1840 16


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