G. Asimakopoulos et al., An anti-inflammatory property of aprotinin detected at the level of leukocyte extravasation, J THOR SURG, 120(2), 2000, pp. 361-369
Citations number
30
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Background: Aprotinin is a serine protease inhibitor used extensively in ca
rdiac operations to reduce postoperative bleeding. It has also been used in
trials aimed at reducing the systemic inflammatory response to cardiopulmo
nary bypass. It remains unclear whether the anti-inflammatory action of apr
otinin is related to its general ability to suppress leukocyte activation o
r whether aprotinin can exercise effects during the leukocyte-endothelial c
ell adhesion cascade.
Methods: We used intravital microscopy to study the 3 main stages of the ad
hesion cascade (leukocyte rolling, firm adhesion, and extravasation) within
the mesenteric microcirculation of rats. This in vivo technique allows leu
kocyte recruitment to be viewed directly through the transparent mesentery
of anesthetized animals,
Results: Aprotinin, given by continuous infusion at a clinically relevant d
ose, exerted no effect on the rolling or firm adhesion responses toward loc
al chemoattractant N-formyl-methyl-leucyl-phenylalanine but significantly i
nhibited extravasation of leukocytes (73% at 40 minutes, P =.03) into surro
unding tissues. In parallel in vitro experiments, aprotinin (used at 200, 8
00, and 1600 kIU/mL) dose dependently inhibited neutrophil transmigration t
hrough cultured endothelial cells in response to 3 different chemoattractan
ts: N-formyl-methyl-leucyl-phenylalanine (P <.001 at 800 and 1600 kIU/mL),
interleukin 8 (P <.05 at 200 kIU/mL and P <.001 at 800 and 1600 kIU/mL), an
d platelet-activating factor (P <.05 at 1600 kIU/mL),
Conclusions: Our studies have therefore revealed a novel anti-inflammatory
mechanism of aprotinin operating at the level of leukocyte extravasation. T
hese findings may be relevant in the prevention of systemic inflammation af
ter cardiopulmonary bypass through the use of protease inhibitors.