Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiorgan, abnormalities in dialysis patients (for example, hepatosplenomegaly, granulomatous hepatitis, cytopenia from hypersplenism) have recently been ascribed to the loading of macrophages (MO) with silicone particles released from the pump segment of dialysis tubing. In the present study, the effect of chronic intravenous or intraperitoneal loading of rats with silicone, polyvinylchloride (PVC) and polyurethane (PU) particles on arachidonic acid metabolism of peritoneal MO and splenic cells was examined in vitro. Intravenous injections of silicone, PVC, or PU particles caused accumulation of the material within the lysosomes of MO of spleen, liver, and lung. Spontaneous release of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) was significantly increased in peritoneal MO of rats injected with silicone, PVC, or PU (Control: 4.27 +/- 0.85 ng PGE2/ml/24 hr; silicone 51.9 +/- 13.2; PVC 57.5 +/- 10.6; PU 28.8 +/- 2.3). Zymosan or LPS stimulated PGE2 release from control MO, but caused no consistent further elevation of high basal PGE2 release from MO after particle loading. Furthermore, increased spontaneous and stimulated TXB2 release was also observed in spleen cells of rats given intravenous injection of silicone particles. It is concluded that storage of plastic particles (silicone, PVC, and PU) by macrophages stimulates arachidonic acid metabolism.
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PMID:Plastic filing from dialysis tubing induces prostanoid release from macrophages. 659 63

Much of the inflammatory response of the body to bloodborne Gram-negative bacteria occurs in the liver and spleen, the major organs that remove these bacteria and their lipopolysaccharide (LPS, endotoxin) from the bloodstream. We show here that LPS undergoes deacylation in the liver and spleen by acyloxyacyl hydrolase (AOAH), an endogenous lipase that selectively removes the secondary fatty acyl chains that are required for LPS recognition by its mammalian signaling receptor, MD-2-TLR4. We further show that Kupffer cells produce AOAH and are required for hepatic LPS deacylation in vivo. AOAH-deficient mice did not deacylate LPS and, whereas their inflammatory responses to low doses of LPS were similar to those of wild type mice for approximately 3 days after LPS challenge, they subsequently developed pronounced hepatosplenomegaly. Providing recombinant AOAH restored LPS deacylating ability to Aoah(-/-) mice and prevented LPS-induced hepatomegaly. AOAH-mediated deacylation is a previously unappreciated mechanism that prevents prolonged inflammatory reactions to Gram-negative bacteria and LPS in the liver and spleen.
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PMID:A host lipase detoxifies bacterial lipopolysaccharides in the liver and spleen. 1732 64