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)

We successfully established a human gastric cancer cell line, HuGC-OOHIRA, from the ascites of a 60-year-old patient with advanced gastric cancer (poorly differentiated adenocarcinoma) complicated by peritonitis carcinomatosa and leukocytosis of unknown origin. Morphologically, the cells were polygonal and adhered weakly to the culture flask. They tended to pile up upon reaching confluence. Chromosome analysis revealed that the cell line has two modes of chromosome number, namely near diploidy and tetraploidy. Double minutes (DMs) were present in abundance in each cell. The doubling time was 25-30 hr. The cell line was successfully transplanted into nude mice, and their peripheral leukocyte counts increased in proportion to the growth of the tumors. At 2 weeks after the transplantation, the serum rG-CSF level was elevated to 2,893 pg/ml. The concentration of human G-CSF in the culture supernatants was an extraordinary high level of 145,380 pg/ml/day. Secretion of GM-CSF and IL-6 was also detected. The intracellular localization of the G-CSF was identified for the first time by immunofluorescence. Moreover, Northern blot analysis detected G-CSF mRNA in this cell line. Anti-recombinant human G-CSF serum suppressed the propagation of HuGC-OOHIRA cell line. Therefore, it is likely that the autocrine growth loop by G-CSF is present in this cell line. This cell line would be very useful for understanding both the cellular and molecular basis for the production of various cytokines such as G-CSF as well as cytokine-dependent tumor proliferation.
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PMID:Establishment and characteristics of a gastric cancer cell line (HuGC-OOHIRA) producing high levels of G-CSF, GM-CSF, and IL-6: the presence of autocrine growth control by G-CSF. 754 2

A 56-year-old woman was admitted to our hospital in January, 1990 because of fever and petechiae. Leukocyte count of peripheral blood showed 41,000/microliters with 89% immature cells, and bone marrow was normocellular with 96.2% immature cells. They were medium to large in size, positive for peroxidase staining, CD-13 and CD-33. Half of them contained azurophilic granules. They showed metachromasia by toluidine blue, contained basophilic granules in electron microscopic examination and reacted to G-CSF, G-CSF and IL-3. She was diagnosed as acute basophilic leukemia and treated with BHAC-DMP and B triple-V regimen, but remission was not attained. She died of peritonitis due to gastrointestinal tract perforation and pneumonia in March, 1990. This is the fifteenth case of acute basophilic leukemia reported in Japan, and the hematological examinations performed in this patient were demonstrated.
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PMID:[Acute basophilic leukemia: a case report]. 768 62

Although sepsis causes significant morbidity and mortality, its basic pathology is still not well understood. We investigated the inflammatory and physiologic alterations of non-lethal sepsis using cecal ligation and puncture (CLP), a model that induces peritonitis due to mixed intestinal flora, reproducing the complex immunology of sepsis. Groups of mice were subjected to CLP (25G needle) or sham surgery, had minimitters implanted to continuously monitor temperature and activity, and were sacrificed daily for 6 days. There was significant hypothermia (6-13 hrs post-surgery), and decreases in activity (to day 4) and weight (to day 3) but no mortality in the CLP group. Blood analyses of the CLP-treated mice showed reduced hemoglobin, platelets, lymphocytes, monocytes, and neutrophils, compared to sham animals. Both groups had nearly equivalent neutrophil influx into the peritoneum. Plasma and peritoneal G-CSF, IL-6, as well as the murine chemokines KC and MIP2-alpha were significantly higher in the CLP-treated mice at day 1. Plasma and peritoneal TNF were low (<70 pg/mL). While there was elevated IL-1beta in the peritoneum of the CLP-treated mice, this cytokine was not detected in the plasma in either treatment group. Cytokines were not detected in the pulmonary airspace of the CLP-treated mice and PMNs were not recruited to this site. Our data shows altered immunopathology in non-lethal sepsis with significant blood and cytokine alterations. Since there was 100% survival, the inflammatory response was appropriate and probably even protective.
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PMID:Immunopathologic responses to non-lethal sepsis. 1044 92

The innate immune system provides essential information about the presence of infectious danger and signals the activation and instruction of adaptive immunity. The present study addressed the question of whether prior exposure of the innate immune system to LPS may modulate host defense against acute septic peritonitis. We show that LPS priming 4 days, but not 2 days, prior to infection enhances bacterial clearance and improves survival of septic peritonitis. Immune protection in day 4 LPS-primed mice was specifically associated with a marked increase in the accumulation and activation of neutrophils at the site of infection. Accumulating neutrophils in day 4 LPS-primed mice exhibited a normal production of reactive oxygen metabolites in response to in vivo exposure to intestinal bacteria. The local increase in neutrophil numbers was found to result from a reduced rate of apoptotic cell death. Inhibition of neutrophil apoptosis in LPS-primed mice was mediated by soluble factor(s) distinct from G-CSF and GM-CSF. Thus, engagement of pattern recognition systems prior to infection may improve host defense by amplifying the effector cell response of innate immunity. The results also provide in vivo evidence that apoptosis of inflammatory cells represents an important process for the control of host defense to infection.
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PMID:Immune protection against septic peritonitis in endotoxin-primed mice is related to reduced neutrophil apoptosis. 1129 54

The selectin family of adhesion molecules and their glycoconjugated ligands are essential for blood polymorphonuclear neutrophil (PMN) extravasation into inflammatory and infectious sites. However, E-selectin ligands on PMNs are not well characterized. We show here that CD44 immunopurified from G-CSF-differentiated 32D cells or from peripheral blood PMNs binds specifically to E-selectin. In contrast, CD44 extracted from bone marrow stromal or brain endothelial cell lines does not interact with E-selectin, suggesting cell-specific posttranslational modifications of CD44. PMN-derived CD44 binding activity is mediated by sialylated, alpha(1,3) fucosylated, N-linked glycans. CD44 enables slow leukocyte rolling on E-selectin expressed on inflamed endothelium in vivo and cooperates with P-selectin glycoprotein ligand-1 to recruit neutrophils into thioglycollate-induced peritonitis and staphylococcal enterotoxin A-injected skin pouch. CD44 extracted from human PMNs also binds to E-selectin. Moreover, we demonstrate that CD44 is hypofucosylated in PMNs from a patient with leukocyte adhesion deficiency type II, suggesting that it contributes to the syndrome. These findings thus suggest broader roles for CD44 in the innate immune response and uncover a potential new target for diseases in which selectins play a prominent role.
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PMID:CD44 is a physiological E-selectin ligand on neutrophils. 1582 84

G-CSF is a hemopoietic growth factor involved in granulocytic differentiation of progenitor cells. In this study, we investigated the effects of PGE2 on G-CSF production in murine peritoneal neutrophils in vitro and in vivo. PGE2 augmented LPS-primed G-CSF release from peritoneal neutrophils. This augmentation was mimicked by a type E prostanoid receptor (EP)2-selective agonist but not by other EP-specific agonists. Indeed, the effect of PGE2 on G-CSF release was abolished in neutrophils isolated from EP2-deficient mice. PGE2 and an EP2 agonist have the ability to stimulate G-CSF gene expression even in the absence of LPS. In the casein-induced peritonitis model, the appearance of G-CSF in the casein-injected peritoneal cavity associated well with the timing of neutrophil infiltration as well as PGE2 levels in exudates, with a peak value at 6 h postinjection. Inhibition of endogenous PG synthesis by indomethacin resulted in a marked decrease in G-CSF content and neutrophil number in the peritoneal cavity. Moreover, EP2-deficient mice exhibited a strikingly reduced G-CSF content in peritoneal exudates with comparable responses in neutrophil migration and local PGE2 production at 6 h postinjection. These results suggest that the PGE2-EP2 system contributes to the local production of G-CSF during acute inflammation.
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PMID:Prostaglandin E2 stimulates granulocyte colony-stimulating factor production via the prostanoid EP2 receptor in mouse peritoneal neutrophils. 1608 35

Elevation of serum sialic acid and the ST6Gal-1 sialyltransferase is part of the hepatic system inflammatory response, but the contribution of ST6Gal-1 has remained unclear. Hepatic ST6Gal-1 elevation is mediated by P1, 1 of 6 promoters regulating the ST6Gal1 gene. We report that the P1-ablated mouse, Siat1DeltaP1, and a globally ST6Gal-1-deficient mouse had significantly increased peritoneal leukocytosis after intraperitoneal challenge with thioglycollate. Exaggerated peritonitis was accompanied by only a modest increase in neutrophil viability, and transferred bone marrow-derived neutrophils from Siat1DeltaP1 mice migrated to the peritonea of recipients with normal efficiency after thioglycollate challenge. Siat1DeltaP1 mice exhibited 3-fold greater neutrophilia by thioglycollate, greater pools of epinephrine-releasable marginated neutrophils, greater sensitivity to G-CSF, elevated bone marrow CFU-G and proliferative-stage myeloid cells, and a more robust recovery from cyclophosphamide-induced myelosuppression. Bone marrow leukocytes from Siat1DeltaP1 are indistinguishable from those of wild-type mice in alpha2,6-sialylation, as revealed by the Sambucus nigra lectin, and in the expression of total ST6Gal-1 mRNA. Together, our study demonstrated a role for ST6Gal-1, possibly from extramedullary sources (eg, produced in liver) in regulating inflammation, circulating neutrophil homeostasis, and replenishing granulocyte numbers.
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PMID:Altered granulopoietic profile and exaggerated acute neutrophilic inflammation in mice with targeted deficiency in the sialyltransferase ST6Gal I. 1684 43

To assess the combined role of G-CSF, GM-CSF, and M-CSF in myeloid cell production, mice deficient in all three myeloid CSFs were generated (G-/-GM-/-M-/- mice). G-/-GM-/-M-/- mice share characteristics found in mice lacking individual cytokines: they are toothless and osteopetrotic and furthermore acquire alveolar proteinosis that is more severe than that found in either GM-/- or G-/-GM-/- mice. G-/-GM-/-M-/- mice have a significantly reduced lifespan, which is prolonged by antibiotic administration, suggesting compromised ability to control bacterial infection. G-/-GM-/-M-/- mice have circulating neutrophils and monocytes, albeit at significantly reduced numbers compared with wild-type mice, but surprisingly, have more circulating monocytes than M-/- mice and more circulating neutrophils than G-/-GM-/- mice. Due to severe osteopetrosis, G-/-GM-/-M-/- mice show diminished numbers of myeloid cells, myeloid progenitors, and B lymphocytes in the bone marrow, but have significantly enhanced compensatory splenic hemopoiesis. Although G-/-GM-/-M-/- mice have a profound deficiency of myeloid cells in the resting peritoneal cavity, the animals mount a moderate cellular response in a model of sterile peritonitis. These data establish that in the absence of G-CSF, GM-CSF, and M-CSF, additional growth factor(s) can stimulate myelopoiesis and acute inflammatory responses.
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PMID:Mice lacking three myeloid colony-stimulating factors (G-CSF, GM-CSF, and M-CSF) still produce macrophages and granulocytes and mount an inflammatory response in a sterile model of peritonitis. 1747 73

The peritoneal macrophage (Mphi) is the site of greatest 12/15-lipoxygenase (12/15-LOX) expression in the mouse; however, its immunoregulatory role in this tissue has not been explored. Herein, we show that 12/15-LOX is expressed by 95% of resident peritoneal CD11b(high) cells, with the remaining 5% being 12/15-LOX(-). 12/15-LOX(+) cells are phenotypically defined by high F4/80, SR-A, and Siglec1 expression, and enhanced IL-10 and G-CSF generation. In contrast, 12/15-LOX(-) cells are a dendritic cell population. Resident peritoneal Mphi numbers were significantly increased in 12/15-LOX(-/-) mice, suggesting alterations in migratory trafficking or cell differentiation in vivo. In vitro, Mphi from 12/15-LOX(-/-) mice exhibit multiple abnormalities in the regulation of cytokine/growth factor production both basally and after stimulation with Staphylococcus epidermidis cell-free supernatant. Resident adherent cells from 12/15-LOX(-/-) mice generate more IL-1, IL-3, GM-CSF, and IL-17, but less CCL5/RANTES than do cells from wild-type mice, while Staphylococcus epidermidis cell-free supernatant-elicited 12/15-LOX(-/-) adherent cells release less IL-12p40, IL-12p70, and RANTES, but more GM-CSF. This indicates a selective effect of 12/15-LOX on peritoneal cell cytokine production. In acute sterile peritonitis, 12/15-LOX(+) cells and LOX products were cleared, then reappeared during the resolution phase. The peritoneal lavage of 12/15-LOX(-/-) mice showed elevated TGF-beta1, along with increased immigration of monocytes/Mphi, but decreases in several cytokines including RANTES/CCL5, MCP-1/CCL2, G-CSF, IL-12-p40, IL-17, and TNF-alpha. No changes in neutrophil or lymphocyte numbers were seen. In summary, endogenous 12/15-LOX defines the resident MPhi population and regulates both the recruitment of monocytes/Mphi and cytokine response to bacterial products in vivo.
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PMID:12/15-Lipoxygenase regulates the inflammatory response to bacterial products in vivo. 1894 Dec 42

NF-kappaB is a major regulator of innate and adaptive immunity. Neutrophilic granulocytes (neutrophils) constitutively express RelA/p65 (Rela), c-Rel (Crel), and p50 (Nfkappab1) but not p52 (Nfkappab2) subunits. In this paper, we describe Crel(-/-)Nfkappab1(-/-)Rela(+/-) mice that have the most severe genetic neutrophil NF-kappaB deficiency compatible with life, Rela(-/-) mice being embryonic lethal. Crel(-/-)Nfkappab1(-/-)Rela(+/-) mice developed spontaneous dermal and intestinal inflammation associated with chronic neutrophilia, elevated CXCL1, and G-CSF. The bone marrow contained fewer nucleated cells and was enriched in myeloid progenitor cells. Neutrophilia was preserved when Crel(-/-)Nfkappab1(-/-)Rela(+/-) bone marrow was transferred into wild-type mice, but mixed bone marrow chimeras receiving wild-type and Crel(-/-)Nfkappab1(-/-)Rela(+/-) bone marrow showed normal circulating neutrophil numbers, excluding an intrinsic proliferation advantage. In mixed bone marrow chimeras, Crel(-/-)Nfkappab1(-/-)Rela(+/-) neutrophils were preferentially mobilized from the bone marrow in response to CXCL1 injection, LPS-induced lung inflammation, and thioglycollate-induced peritonitis. Crel(-/-)Nfkappab1(-/-)Rela(+/-) neutrophils expressed higher levels of the CXCL1 receptor CXCR2 both under resting and stimulated conditions and failed to downregulate CXCR2 during inflammation. Treatment with an anti-CXCR2 Ab abolished preferential mobilization of Crel(-/-)Nfkappab1(-/-)Rela(+/-) neutrophils in peritonitis in mixed chimeric mice and neutrophilia in Crel(-/-)Nfkappab1(-/-)Rela(+/-) mice. We conclude that severe NF-kappaB deficiency facilitates neutrophil mobilization, which causes elevated numbers of preactivated neutrophils in blood and tissues, leading to spontaneous inflammation. These neutrophil effects may limit the usefulness of global NF-kappaB inhibitors for the treatment of inflammatory diseases.
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PMID:Defective regulation of CXCR2 facilitates neutrophil release from bone marrow causing spontaneous inflammation in severely NF-kappa B-deficient mice. 2051 47


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