Document 0016
 DOCN  M9580016
 TI    Influence of anti-inflammatory drugs on adhesion of neutrophils to
       endothelial cells cultured on microcarriers: a novel in vitro system as
       an alternative to animal experimentation.
 DT    9506
 AU    Zwahlen RD; Holden WJ; Wyder-Walther M; Holub M; Moiola F; Institute of
       Veterinary Pathology, University of Bern,; Switzerland.
 SO    Zentralbl Veterinarmed A. 1994 Nov;41(9):671-82. Unique Identifier :
       AIDSLINE MED/95250393
 AB    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.
 DE    Animal  *Animal Testing Alternatives  Anti-Inflammatory Agents,
       Non-Steroidal/*PHARMACOLOGY  Anti-Inflammatory Agents,
       Steroidal/*PHARMACOLOGY  Cattle  Cell Adhesion/DRUG EFFECTS/PHYSIOLOGY
       Cells, Cultured  Endothelium, Vascular/CYTOLOGY/*DRUG EFFECTS  Female
       Neutrophils/CYTOLOGY/*DRUG EFFECTS  Support, Non-U.S. Gov't  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).