PMID- 7824814
OWN - NLM
STAT- MEDLINE
DCOM- 19950214
LR  - 20180216
IS  - 0025-7931 (Print)
IS  - 0025-7931 (Linking)
VI  - 61
IP  - 6
DP  - 1994
TI  - The anti-inflammatory drug nimesulide inhibits neutrophil adherence to and 
      migration across monolayers of cytokine-activated endothelial cells.
PG  - 336-41
AB  - Neutrophil migration through the microvascular endothelium represents a 
      fundamental event for the cell accumulation at sites of tissue injury. Owing to 
      their capacity to modify the structural and functional characteristics of 
      endothelial cells, inflammatory cytokines such as interleukin-1 (IL-1) and tumor 
      necrosis factor-alpha (TNF alpha) play a pivotal role in directing circulating 
      neutrophils away from the bloodstream to the interstitial tissue. In order to 
      study neutrophil transendothelial migration, human umbilical vein endothelial 
      cells were grown to confluence on the polycarbonate filter of two-compartment 
      migration chambers. Pretreatment of the endothelial cell monolayers with TNF 
      alpha for 4 h resulted in rapid migration of approximately 50% of subsequently 
      added neutrophils across the layers. In contrast, < 10% of added neutrophils 
      penetrated untreated endothelial monolayers. Using TNF alpha-treated endothelium, 
      neutrophil transmigration was inhibited by the methane sulfonanilide 
      anti-inflammatory drug nimesulide. Moreover, neutrophil adherence to TNF 
      alpha-treated endothelial monolayers, cultured in microtiter wells, was markedly 
      reduced by nimesulide. A linear correlation between the drug-dependent inhibition 
      of neutrophil transmigration and neutrophil adherence was found. Finally, 
      nimesulide did not interfere with the TNF alpha ability to convert resting 
      endothelium into a pro-adhesive and pro-locomotory cell layer. The data suggest 
      that nimesulide reduces neutrophil transendothelial migration primarily by 
      limiting the cell anchorage to the TNF alpha-activated endothelium. Therefore, 
      the drug has the potential to down-regulate neutrophil extravasation and, in 
      turn, the burden of neutrophil oxidants and proteases leading to tissue injury at 
      sites of inflammation.
FAU - Dapino, P
AU  - Dapino P
AD  - Department of Internal Medicine, University of Genova Medical School, Italy.
FAU - Ottonello, L
AU  - Ottonello L
FAU - Dallegri, F
AU  - Dallegri F
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - Respiration
JT  - Respiration; international review of thoracic diseases
JID - 0137356
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Sulfonamides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - V4TKW1454M (nimesulide)
SB  - IM
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Cell Adhesion/drug effects
MH  - Cell Movement/drug effects
MH  - Cells, Cultured
MH  - Endothelium, Vascular/*physiology
MH  - Humans
MH  - Neutrophils/*drug effects/physiology
MH  - Sulfonamides/*pharmacology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1994/01/01 00:00
MHDA- 1994/01/01 00:01
CRDT- 1994/01/01 00:00
PHST- 1994/01/01 00:00 [pubmed]
PHST- 1994/01/01 00:01 [medline]
PHST- 1994/01/01 00:00 [entrez]
AID - 10.1159/000196365 [doi]
PST - ppublish
SO  - Respiration. 1994;61(6):336-41. doi: 10.1159/000196365.