title: Liver ischemia/reperfusion induces an increase of microvascular leukocyte flux, but not heterogeneity of leukocyte trafficking.
abstract: Leukocytic response plays a major role in the manifestation of hepatic ischemia/reperfusion (I/R) injury. To clarify whether post-ischemic hepatic leukocyte accumulation is based on increased leukocyte flux to the hepatic tissue due to systemic inflammation or chemoattractant activities or whether it represents solely a local tissue response without changing overall leukocyte flux and trafficking characteristics through the microvasculature, we studied acinar and sinusoidal leukocyte flux and distribution in rat livers in vivo both under normal (sham, n = 8) and post-ischemic (60' ischemia/75' reperfusion) conditions (I/R, n = 8), using fluorescence epi-illumination microscopy (rhodamine-6G). Hepatic ischemia/reperfusion significantly (p < 0.05) increased acinar leukocyte flux (58.4 +/- 20.9 cells/min vs 36.4 +/- 12.8 cells/min in sham controls); however, it did not exhibit increased heterogeneity of acinar leukocyte distribution, as indicated by the unchanged coefficient of variance (CV) of 0.36 +/- 0.16 (sham controls: 0.31 +/- 0.14). In parallel, analysis of individual sinusoidal leukocyte flux demonstrated significantly (p < 0.05) higher values (8.9 +/- 3.7 cells/min) after ischemia/reperfusion when compared with sham controls (5.7 +/- 1.9 cells/min), which, however, was not associated with increased heterogeneity of sinusoidal leukocyte trafficking (CV: 0.85 +/- 0.15 vs 0.85 +/- 0.16 in sham controls) and manifestation of preferential pathways. Analysis of blood cell count did not demonstrate an overall increase of total blood leukocyte count; however, an increased (p < 0.01) fraction of polymorphonuclear leukocytes (65.2 +/- 11.2%) and stab cells (9.5 +/- 7.9%) during post-ischemic reperfusion when compared with sham controls (8.8 +/- 3.5% and 0.2 +/- 0.4%) was demonstrated. Thus, the increase of hepatic leukocyte flux after ischemia/reperfusion may be the result of both the manifestation of a systemic inflammatory response and the increase of local chemoattractant activities, such as the production and release of the cytokine-induced neutrophil chemoattractant of the IL-8 family.
authors.affiliation: Institute for Clinical & Experimental Surgery, University of Saarland, Homburg/Saar, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Vollmar
authors.forename: S
authors.initials: S
authors.lastname: Richter
authors.forename: M D
authors.initials: MD
authors.lastname: Menger
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002452:Cell Count; D007962:Leukocytes / Q000473:pathology*; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008297:Male; D008833:Microcirculation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood* / Q000473:pathology