Abstract |
Pharmacological control of inflammation by steroidal ( SAIDs) and nonsteroidal ( NSAIDs) antiinflammatory drugs is of substantial clinical importance. To reduce the number of animals used in pharmacological and toxicological evaluation of these drugs we developed a novel assay to determine adhesion of bovine neutrophils (PMN) to bovine aortic endothelial cells (BAEC) cultured on microcarriers in a flow-through system. Pretreatment of BAEC with thrombin (10(-7)-10(-4) M) led to a dose-dependent increase of PMN-adhesion (10(-6)-10(-4) M:P < 0.05); platelet-activating factor (10(-9) M) and 1:200 diluted zymosan-activated serum (ZAS) had similar effects (P < 0.001). Pretreatment of PMN with SAIDs (50.9 and 509 microM dexamethasone, 12.2 and 24.4 microM flumethasone) did inhibit adhesion to ZAS-treated BAEC dose-dependently. Pretreatment of PMN with NSAIDs had a less consistent influence on adhesion to ZAS-stimulated BAEC. While phenylbutazone (0.33 and 3.3 mM), diclofenac (0.392 and 0.574 mM), indomethacine (0.436 and 0.872 mM), and acetylsalicylic acid (3.47 and 16.94 mM) induced dose-dependent inhibition of PMN-adhesion to ZAS-treated BAEC, piroxicam (0.377 and 0.754 mM) inhibited PMN-adhesion strongly (P < 0.001) but not dose-dependently, and ketoprofene (0.614 and 1.228 mM) had no effect on PMN-adhesion. The method presented here is efficient for evaluating the pharmacological modulation of PMN interaction with endothelial cells, and useful for studying further aspects of endothelial cell biology.
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Authors | R D Zwahlen, W J Holden, M Wyder-Walther, M Holub, F Moiola |
Journal | Zentralblatt fur Veterinarmedizin. Reihe A
(Zentralbl Veterinarmed A)
Vol. 41
Issue 9
Pg. 671-82
(Nov 1994)
ISSN: 0514-7158 [Print] Germany |
PMID | 7732745
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Steroids
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Topics |
- Animal Testing Alternatives
- Animals
- Anti-Inflammatory Agents
(pharmacology)
- Anti-Inflammatory Agents, Non-Steroidal
(pharmacology)
- Cattle
- Cell Adhesion
(drug effects, physiology)
- Cells, Cultured
- Endothelium, Vascular
(cytology, drug effects)
- Female
- Neutrophils
(cytology, drug effects)
- Steroids
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