HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Effects of uridine, isomatitol and 4-thiouridine on in vitro cell adhesion and in vivo effects of 4-thiouridine in a lung inflammation model.

Abstract
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.
AuthorsSrinivas Uppugunduri, Chamilly Gautam
JournalInternational immunopharmacology (Int Immunopharmacol) Vol. 4 Issue 9 Pg. 1241-8 (Sep 2004) ISSN: 1567-5769 [Print] Netherlands
PMID15251120 (Publication Type: Journal Article)
Chemical References
  • Buffers
  • Culture Media
  • Polysaccharides
  • Tumor Necrosis Factor-alpha
  • Thiouridine
  • sephadex
  • Dextrans
  • Uridine
Topics
  • Animals
  • Bronchoalveolar Lavage Fluid (chemistry, cytology)
  • Buffers
  • Cell Adhesion (drug effects)
  • Cell Separation
  • Culture Media
  • Dextrans
  • Humans
  • Lung (pathology)
  • Male
  • Molecular Weight
  • Neutrophils (immunology)
  • Pneumonia (chemically induced, drug therapy, pathology)
  • Polysaccharides (toxicity)
  • Rats
  • Rats, Sprague-Dawley
  • Thiouridine (pharmacology, therapeutic use)
  • Tumor Necrosis Factor-alpha (metabolism)
  • Umbilical Cord (cytology)
  • Uridine (pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: