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.

• Authors: Srinivas Uppugunduri, Chamilly Gautam
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 4 Issue 9 Pg. 1241-8 (Sep 2004) ISSN: 1567-5769 [Print] Netherlands
• PMID: 15251120 (Publication Type: Journal Article)

Chemical References

• Buffers
• Culture Media
• Dextrans
• Polysaccharides
• Tumor Necrosis Factor-alpha
• Thiouridine
• sephadex
• 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)