Inhibition of neutrophil L-selectin shedding: a potential anti-inflammatory effect of aprotinin.
The cardiopulmonary bypass (CPB)-related inflammatory response involves leucocyte activation and increased leucocyte-endothelial cell interaction. L-selectin is an adhesion molecule expressed on the surface of leucocytes which participates in the initial rolling step of the leucocyte-endothelial cell adhesion cascade. L-selectin is proteolytically cleaved off the surface of leucocytes when they become activated, an event that is regarded as a marker of leucocyte activation. Aprotinin is a protease inhibitor that has been used in cardiac surgery as a haemostatic agent and also exhibits certain anti-inflammatory properties. In this study, peripheral venous blood from volunteers was pre-incubated with aprotinin at 200, 800 and 1600 kallikrein inhibiting units (kiu)/ml and stimulated with the chemoattractants N-formyl-methyl-leucyl-phenylalanine (fMLP) or platelet activating factor (PAF). Surface expression of L-selectin on neutrophils was measured using a monoclonal antibody and flow cytometry. The results demonstrate that aprotinin inhibits shedding of L-selectin in a dose-dependent fashion (p=0.0278 and 0.0005, respectively, at 800 and 1600 kiu/ml for fMLP-stimulated shedding; p=0.0017 and 0.0010, respectively, at 200 and 800 kiu/ml for PAF-stimulated shedding). This effect may be of significance with respect to the anti-inflammatory action of aprotinin in patients undergoing CPB.
Asimakopoulos
G
G
British Heart Foundation Cardiac, Surgery Unit, National Heart and Lung Institute, Imperial College School of Medicine at Hammersmith Hospital, London, UK.
Taylor
K M
KM
Haskard
D O
DO
Landis
R C
RC
D007611:Aprotinin / Q000494:pharmacology; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D019041:L-Selectin / Q000187:drug effects* / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology
D010972:Platelet Activating Factor; D015842:Serine Proteinase Inhibitors; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D007611:Aprotinin