Ischemic limb preconditioning downregulates systemic inflammatory activation.
We examined local and systemic antiinflammatory consequences of ischemic preconditioning (IPC) in a rat model of limb ischemia-reperfusion (I-R) by characterizing the leukocyte-endothelial interactions in the periosteum and the expression of adhesion molecules playing a role in leukocyte-mediated inflammatory processes. IPC induction (2 cycles of 10 min of complete limb ischemia and 10 min of reperfusion) was followed by 60 min of ischemia/180 min of reperfusion or sham-operation. Data were compared with those on animals subjected to I-R and sham-operation. Neutrophil leukocyte-endothelial cell interactions (intravital videomicroscopy), intravascular neutrophil activation (CD11b expression changes by flow cytometry), and soluble and tissue intercellular adhesion molecule-1 (ICAM-1; ELISA and immunohistochemistry, respectively) expressions were assessed. I-R induced enhanced leukocyte rolling and adherence in the periosteal postcapillary venules after 120 and 180 min of reperfusion. This was associated with a significantly enhanced CD11b expression (by approximately 80% and 72%, respectively) and moderately increased soluble and periosteal ICAM-1 expressions. IPC prevented the I-R-induced increases in leukocyte adherence and CD11b expression without influencing the soluble and tissue ICAM-1 levels. The results show that limb IPC exerts not only local, but distant antiinflammatory effects through significant modulation of neutrophil recruitment.
Szabó
Andrea
A
Institute of Surgical Research, University of Szeged, H-6720 Szeged, Pécsi u. 6, Hungary. sza@expsur.szote.u-szeged.hu
Varga
Renáta
R
Keresztes
Margit
M
Vízler
Csaba
C
Németh
István
I
Rázga
Zsolt
Z
Boros
Mihály
M
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D006614:Hindlimb / Q000098:blood supply* / Q000276:immunology*; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019194:Ischemic Preconditioning; D036904:Leukocyte Rolling / Q000276:immunology; D008297:Male; D008833:Microcirculation / Q000276:immunology; D018715:Microscopy, Video; D009504:Neutrophils / Q000276:immunology; D010521:Periosteum / Q000098:blood supply / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000276:immunology; D015427:Reperfusion Injury / Q000276:immunology* / Q000517:prevention & control*; D013977:Tibia / Q000098:blood supply / Q000276:immunology; D014699:Venules / Q000276:immunology
D039481:CD11b Antigen; D018799:Intercellular Adhesion Molecule-1