Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031154 (peritonitis)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutrophil emigration during an inflammatory response is mediated through interactions between adhesion molecules on endothelial cells and neutrophils. P-Selectin mediates rolling or slowing of neutrophils, while intercellular adhesion molecule-1 (ICAM-1) contributes to the firm adhesion and emigration of neutrophils. Removing the function of either molecule partially prevents neutrophil emigration. To analyze further the role of P-selectin and ICAM-1, we have generated a line of mice with mutations in both of these molecules. While mice with either mutation alone show a 60-70% reduction in acute neutrophil emigration into the peritoneum during Streptococcus pneumoniae-induced peritonitis, double mutant mice show a complete loss of neutrophil emigration. In contrast, neutrophil emigration into the alveolar spaces during acute S. pneumoniae-induced pneumonia is normal in double mutant mice. These data demonstrate organ-specific differences, since emigration into the peritoneum requires both adhesion molecules while emigration into the lung requires neither. In the peritoneum, P-selectin-independent and ICAM-1-independent adhesive mechanisms permit reduced emigration when one of these molecules is deficient, but P-selectin-independent mechanisms cannot lead to ICAM-1-independent firm adhesion and emigration.
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PMID:P-selectin/ICAM-1 double mutant mice: acute emigration of neutrophils into the peritoneum is completely absent but is normal into pulmonary alveoli. 753 94

The initial rolling interaction of leukocytes with the blood vessel wall during leukocyte trafficking has been postulated to rely on members of the selectin family of adhesion molecules. Two selectins, E-selectin and P-selectin, have been identified that are expressed on activated endothelial cells. Mice deficient in E-selectin expression have been produced in order to examine the role of this selectin in leukocyte trafficking. Mice homozygous for an E-selectin null mutation were viable and exhibited no obvious developmental alterations. E-selectin-deficient mice displayed no significant change in the trafficking of neutrophils in several models of inflammation. However, blocking both endothelial selectins by treatment of the E-selectin-deficient animals with an anti-murine P-selectin antibody, 5H1, significantly inhibited neutrophil emigration in two distinct models of inflammation. While neutrophil accumulation at early times during thioglycollate-induced peritonitis was dependent on P-selectin, neutrophil accumulation at later time points was blocked by 5H1 only in E-selectin-deficient mice but not in wild-type mice. Similarly, edema as well as leukocyte accumulation in a model of delayed-type hypersensitivity in the skin was almost completely prevented by blockade of P-selectin function with 5H1 in the E-selectin-deficient mice while the same treatment had no effect in wild-type mice. These data demonstrate that the majority of neutrophil migration in both models requires an endothelial selectin but that E-selectin and P-selectin are functionally redundant. These data have important implications in the use of selectin antagonists in the treatment of inflammatory disease.
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PMID:Characterization of E-selectin-deficient mice: demonstration of overlapping function of the endothelial selectins. 754 6

P-selectin is expressed on the surfaces of activated platelets and endothelium where it mediates binding to leukocytes. P-selectin-deficient mice were shown to exhibit peripheral neutrophilia (Mayadas et al: Cell 74:541, 1993). We now show that this is not caused by changes in bone marrow precursors nor by a lack of neutrophil margination. Both P-selectin-positive and -negative animals displayed similar increases in peripheral blood neutrophil numbers after injection of epinephrine. However, clearance of 51Chromium-labeled neutrophils is delayed in mice deficient for P-selectin, indicating that the neutrophilia is at least in part the result of delayed removal. We detected no obvious alterations in lymphocyte differentiation, distribution, or adhesion to high endothelial venules in peripheral lymph nodes. Through intravital microscopy, we examined the impact of P-selectin deficiency on leukocyte/endothelial interaction beyond the initial stages of inflammation. Four hours after the administration of an inflammatory irritant, leukocyte rolling was observed even in the absence of P-selectin. There were significantly fewer rolling cells relative to wild-type mice, and their velocity was reduced. Moreover, in the peritonitis model, the number of peritoneal macrophages in wild-type mice increased threefold at 48 hours, whereas the macrophages in the mutant mice remained near baseline levels. Thus, whereas P-selectin is known to be involved in early stages of an inflammatory response, our results indicate that it is additionally responsible for leukocyte rolling and macrophage recruitment in more prolonged tissue injury.
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PMID:Blood cell dynamics in P-selectin-deficient mice. 754 95

A variety of adhesion molecules have been identified which mediate the interaction of leukocytes with endothelial cells. In order to define the role of individual molecules in inflammation we have produced lines of mice which are deficient in the synthesis of specific adhesion molecules. Null mutations were introduced into the genes encoding E-selectin or vascular cell adhesion molecule-1 (VCAM-1) in embryonic stem cells and these cells were used to produce lines of mice carrying the mutation. E-selectin-deficient mice were viable and exhibited no developmental defects. The roles of E- and P-selectin in the influx of neutrophils were examined using these mice. The data suggest that the two selectins are functionally redundant in mediating neutrophil emigration in a model of chemically induced peritonitis. VCAM-1-deficient mice are not viable. Analysis of VCAM-1 gene expression in wild-type embryos and phenotypic analysis of VCAM-1 -/- embryos suggests that VCAM-1 is required for development of the extraembryonic circulatory system and the embryonic heart.
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PMID:Creation and characterization of E-selectin- and VCAM-1-deficient mice. 758 31

The selectins are cell adhesion molecules whose carbohydrate-binding domain (C-type lectin) is thought to be involved in leukocyte adhesion to activated vascular endothelium in the inflammatory process. A series of peptides, based on a conserved region (48YYWIGIRK55-NH2) of the lectin domain of E-, L- and P-selectins, were analysed for their ability to block selectin-mediated cell adhesion in vitro, and neutrophil infiltration into sites of inflammation in vivo. The peptides inhibited the adhesion of myeloid cells to recombinant forms of E- and P-selectin. The adhesion of myeloid cells to human endothelial cells, stimulated to express E-selectin, was also inhibited by the peptides. Finally, the peptides blocked the adhesion of lymphocytes, expressing L-selectin, to high endothelial venules in lymph nodes which contain the ligand for L-selectin. A clear structure-activity relationship was established when peptides of different amino acid chain lengths were tested in these assays. Peptides lacking tyrosine residues (e.g. WIGIR-NH2) at their amino terminus were poor inhibitors of selectin-mediated cell adhesion in vitro. The peptides that were found to be inhibitors of cell adhesion in vitro were also found to inhibit (up to 70%) neutrophil infiltration into sites of inflammation in a thioglycollate-induced peritonitis mouse model system. They also significantly reduced (> 50%) the migration of neutrophils into cytokine-treated skin. These results strongly suggest that compounds based on these tyrosine-containing, selectin-derived peptides could be used as anti-inflammatory therapeutic agents.
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PMID:Peptides inhibit selectin-mediated cell adhesion in vitro, and neutrophil influx into inflammatory sites in vivo. 856 45

The selectins are inducible adhesion molecules critically important for the inflammatory response. We investigate here the functional effects of three monoclonal antibodies (MoAbs) raised against murine E-selectin (9A9, 10E6, and 10E9.6) on neutrophil recruitment in vivo, leukocyte rolling and circulating leukocyte concentrations in vivo, and adhesion of myeloid cells to E-selectin transfectants and recombinant E-selectin-IgG fusion protein in vitro. MoAbs 9A9 and 10E6 map to the lectin and epidermal growth factor (EGF)-like domains of murine E-selectin, whereas 10E9.6 binds to the consensus repeat region. 10E9.6 blocked neutrophil recruitment in a model of thioglycollate-induced peritonitis in Balb/c mice by more than 90% but had no effect in C57BL/6 mice. 9A9 and 10E6 blocked neutrophil recruitment in this assay only when combined with a P-selectin antibody, 5H1. Neither 9A9 nor 10E9.6 alone blocked leukocyte rolling in tumor necrosis factor-alpha-treated venules of Balb/c mice, but 9A9 almost completely inhibited leukocyte rolling when combined with the function-blocking murine P-selectin MoAb, RB40.34. In contrast, 10E9.6 had no effect on leukocyte rolling in RB40.34-treated Balb/c or C57BL/6 mice. 10E9.6 did not affect adhesion of myeloid cells to E-selectin transfectants or attachment, rolling, and detachment of myeloid cells to murine E-selectin-IgG fusion protein. However, adhesion was completely blocked in the same assays by 9A9. Taken together, these results indicate that E-selectin serves a function, other than rolling, that appears to be critically important for neutrophil recruitment to inflammatory sites in Balb/c mice.
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PMID:Differential effect of E-selectin antibodies on neutrophil rolling and recruitment to inflammatory sites. 910 22

Neutrophil recruitment into systemic inflammatory sites in vivo is thought to be initiated by selectin-mediated endothelial adherence. The effect of fucoidan (natural sulfated polymer of L-fucose) on the selectin dependent PMN migration into rat peritoneum following the induction of inflammation by peptone injection was studied. Peritonitis was characterized by an increase in the total cell number (from 45.3 x 10(6) to 91.6 x 10(6)/rat), and by highly elevated PMN content (from 0.2% to 58%) in the rat peritoneal cavity 3 h after peptone injection. Intravenous administration of fucoidan was found to reduce, in a dose-dependent manner, neutrophil migration into peritoneum. Fucoidan in a dose as low as 0.8 mg per rat caused 96.8% reduction of neutrophil extravasation. The inhibitory effect of fucoidan was also dependent on the time intervals between the peptone and fucoidan injections. The maximal inhibitory effect of fucoidan was observed within the first 15 min after the induction of peritonitis and it was maintained at a level of 80% during 1.5 h. Administration of fucoidan 2.5 h after peptone injection had practically no effect on PMN extravasation. Since P-selectin is known to play a key role at the earlier stages of PMN extravasation, it was suggested that the inhibitory effect of fucoidan was mostly due to its interaction with P-selectin. The in vitro experiments demonstrated the high affinity of fucoidan for both isolated P-selectin and P-selectin in plasma membranes of activated platelets.
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PMID:Fucoidan inhibits leukocyte recruitment in a model peritoneal inflammation in rat and blocks interaction of P-selectin with its carbohydrate ligand. 935 Mar 52

To determine the relative in vivo importance of endothelial expressed adhesion molecules to eosinophil rolling, adhesion, and transmigration, we have induced eosinophilic peritonitis using ragweed allergen in P-selectin-deficient, intracellular adhesion molecule-1 (ICAM-1)-deficient and control wild-type mice. Circulating leukocytes visualized by intravital microscopy exhibited reduced rolling and firm adhesion in P-selectin-deficient mice and reduced firm adhesion in ICAM-1-deficient mice. Eosinophils exhibited reduced rolling and firm adhesion to endothelium in P-selectin-deficient mice. Eosinophil recruitment in P-selectin-deficient mice ( approximately 75% inhibition of eosinophil recruitment) and ICAM-1-deficient mice ( approximately 67% inhibition of eosinophil recruitment) was significantly reduced compared with wild-type mice. Eosinophil recruitment was not completely inhibited in P-selectin/ICAM-1 double-mutant mice (eosinophil recruitment inhibited approximately 62%). However, pretreatment of P-selectin/ICAM-1-deficient mice with an anti-vascular cell adhesion molecule (VCAM) antibody induced near complete inhibition of eosinophil recruitment. Overall, these studies show that eosinophil rolling and firm adhesion is significantly reduced in P-selectin-deficient mice and that P-selectin, ICAM-1, and VCAM are important to eosinophil peritoneal recruitment after ragweed challenge.
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PMID:Inhibition of eosinophil rolling and recruitment in P-selectin- and intracellular adhesion molecule-1-deficient mice. 953 95

The inhibitory effects of sulfated polysaccharides-fucoidan and heparin on P-selectin-ligand interaction in vitro and on the ability of fucoidan to inhibit the leukocyte extravasation in rat peritonitis were studied. The lectin activity of P-selectin in vitro was based on its ability to bind lectin-labeled synthetic ligand, Sialyl-Lea/x, conjugated with polyacrylamide (PAA). Fucoidan and heparin inhibited binding of labeled ligand to both purified P-selectin and the activated platelets expressing P-selectin on their surface. The inhibitory effect of fucoidan 100-fold higher than that of heparin. As P-selectin plays an important role at an earlier stage of the inflammation process, the antiinflammatory action of fucoidan on P-selectin-dependent peritonitis in rats was studied. Peritonitis was induced by intraperitoneal injection of the peptone solution and was characterized by an increase in total cell number and neutrophil percentage in rat peritone exudate. Intravenous injection of fucoidan was found to cause a dose- and time-dependent reduction of neutrophil extravasation into inflamed peritoneum. The minimal dose of fucoidan, that was able to produce 96.8 +/- 2.9% inhibition of neutrophil extravasation--if administered within the first 15 min after peptone-B was 0.8 mg per rat. Significant effect of fucoidan injection (about 80% inhibition) was also obtained 1.5 h after the induction of inflammation. Fucoidan administered 2.5 h after peptone had virtually no effect on neutrophil extravasation. The data obtained show that fucoidan blocks the inflammation process at its earlier stages--most probably at the expense of its interaction with P-selectin.
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PMID:[Sulfated polysaccharides as inhibitors of receptor activity of P-selectin and P-selectin-dependent inflammation]. 963 15

To investigate the requirements for adhesion molecules in neutrophil emigration during peritonitis, mice received intraperitoneal injections of Streptococcus pneumoniae while the functions of multiple adhesion molecules were blocked. Emigration after 4 h was compromised by antibodies against ICAM-1 or genetic deficiency of ICAM-1. Anti-CD11a/CD18 antibodies decreased emigration in ICAM-1 mutant mice, suggesting that ICAM-1 independent emigration requires CD11/CD18 complexes. In contrast, mice mutant in ICAM-1 plus E-selectin showed no defect in emigration, suggesting that E-selectin commits neutrophils to an ICAM-1-dependent pathway during streptococcal peritonitis. However, in mutant mice lacking the three endothelial adhesion molecules E-selectin, P-selectin, and ICAM-1, emigration after 4 h was significantly compromised. Thus, P-selectin is essential to ICAM-1- and E-selectin-independent acute peritoneal inflammation. After 24 h of peritonitis, there were no differences between WT and E-selectin/P-selectin/ICAM-1 mutant mice, demonstrating that these endothelial adhesion molecules are not essential to neutrophil emigration during later stages of peritonitis.
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PMID:Combinatorial requirements for adhesion molecules in mediating neutrophil emigration during bacterial peritonitis in mice. 973 54


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