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Effects of uridine,...
Effects of uridine, isomatitol and 4-thiouridine on in vitro cell adhesion and in vivo effects of 4-thiouridine in a lung inflammation model.
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- Uppugunduri, Srinivas (author)
- Östergötlands Läns Landsting,Linköpings universitet,Klinisk kemi,Hälsouniversitetet
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- Gautam Evaldsson, Chamilly (author)
- Linköpings universitet,Klinisk kemi,Hälsouniversitetet
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(creator_code:org_t)
- Elsevier BV, 2004
- 2004
- English.
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In: International Immunopharmacology. - : Elsevier BV. - 1567-5769 .- 1878-1705. ; 4:9, s. 1241-1248
- Related links:
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http://urn.kb.se/res...
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https://doi.org/10.1...
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Abstract
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- Since leukocyte adhesion to endothelial cells is crucial for extravasation of leukocytes to sites of inflammation, inhibition of cell-cell adhesion has been suggested as a means to achieve selective modulation of the immune system. We have, using a static in vitro adhesion assay involving adhesion of granulocytes to tumor necrosis factor alpha (TNFalpha)-stimulated human umbilical vein endothelial cells (HUVEC), found three substances--uridine, isomaltitol and 4-thiouridine-that, independently and significantly, reduced leukocyte adhesion by approximately 30-65%. 4-Thiouridine was also tested in an in vivo model of Sephadex (SDX)-induced lung inflammation with Sprague-Dawley rats. Intratracheal instillation of Sephadex (5 mg/kg) alone resulted in a dramatic increase in lung edema and total leukocyte count after 24 h. A differential count of bronchoalveolar lavage (BAL) cells indicated an increased influx of macrophages, eosinophils and neutrophils. Co-administration of 4-thiouridine significantly reduced lung edema by 38%. There was also a significant reduction of the total leukocyte count by 58%. The differential leukocyte count indicated that eosinophil influx alone was reduced by 70%. After Sephadex challenge, we found elevated levels of TNFalpha--an important inflammatory mediator--in the bronchoalveolar lavage fluid (BALF). TNFalpha levels were significantly reduced by more than 80% by co-administration of 4-thoiuridine. These results suggest that uridine, isomaltitol and, especially, 4-thiouridine affect adhesion between leukocytes and activated endothelium, and warrant further in vitro and in vivo studies.
Keyword
- Inflammation; Adhesion; TNFa; Uridine; Isomaltitol; 4-thiouridine
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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