The inhibitory effect of tenidap on leukocyte-endothelial cell adhesion.
OBJECTIVE
Adhesion of neutrophils to vascular endothelial cells (EC) and neutrophil chemotaxis are essential processes which enable neutrophils to infiltrate the tissues. They represent potentially important targets for therapeutic intervention in inflammatory diseases. This study was conducted to test the effect of tenidap sodium on neutrophil adhesion and chemotaxis.


METHODS
Adhesion of 51Cr sodium chromate labelled neutrophils to umbilical vein EC monolayers was assayed in 96-well microtiter plates. Neutrophil chemotaxis was measured in Boyden microchemotaxis chambers.


RESULTS
Tenidap sodium caused a dose related inhibition of neutrophil adhesion to EC, with 50 microM tenidap resulting in 51.8 +/- 4.0% (mean +/- SEM) inhibition of unstimulated adhesion and 46.1 +/- 2.6% inhibition of formyl-methionyl-leucyl-phenylalanine (FMLP) stimulated adhesion. A marked reduction in neutrophil chemotaxis in response to FMLP was also observed, with 50 microM and 100 microM tenidap leading to 83.4 +/- 8.5% and 92.1 +/- 8.5% (mean +/- SEM) inhibition respectively. The effect of tenidap on neutrophil adhesion to EC was not seen when neutrophils were preincubated with tenidap and then washed before adding to EC monolayers, suggesting an action upon surface molecules or in the cell membrane. Aspirin, indomethacin and phenylbutazone did not inhibit leukocyte adhesion, indicating that this action of tenidap may not be a consequence of inhibition of cyclooxygenase. The potency of tenidap was reduced by inclusion of serum or plasma in the culture medium, presumably due to protein binding.


CONCLUSIONS
It is possible that inhibition of leukocyte-EC adhesion by tenidap sodium may contribute to the antiinflammatory effects of the drug.
Kyan-Aung
U
U
Rheumatology Unit, United Medical School (UMDS), Guy's Hospital, London, United Kingdom.
Lee
T H
TH
Haskard
D O
DO
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D000078183:Oxindoles
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007211:Indoles; D000078183:Oxindoles; C062866:tenidap