HEPATIC NEUTROPHIL SEQUESTRATION IN EARLY SEPSIS

Abstract

Abdominal sepsis was produced by cecal ligation and puncture (CLP) in rats to observe neutrophil (PMN) migration into the liver and assess the functional alteration in circulating PMNs, liver sequestered PMNs, and Kupffer cells. 7 h following CLP, rats demonstrated severe leukopenia and major amount of PMNs sequestered into the liver (17.0 +/- 5.5 x 10(6) vs. 3.1 +/- 1.6 x 10(6) in sham-operated rats, p < .01). Light microscopic evidence demonstrated the presence of such PMNs in the sinusoids and in the liver parenchyma. By 20 h following CLP, the number of PMNs in the liver was not different from sham controls. CD11b/c expression on circulating PMNs was significantly upregulated from 1.6 +/- .3 to 7.8 +/- .9 mean channel fluorescence (MCF) in 7 h CLP rats. Liver-sequestered PMNs showed further enhancement of CD11b/c expression to 10.4 +/- 1.9 MCF than the circulating PMNs. However, in the late septic rats, CD11b/c expression on circulating PMNs 2.9 +/- .5 MCF returned to the control level of 1.9 +/- .7 MCF. Liver-sequestered PMNs and Kupffer cells in septic rats exhibited remarkably enhanced phagocytic activities 53.0 +/- 10.8 and 56.9 +/- 7.7% phagocytosis, respectively, regardless of the suppression of phagocytosis in circulating PMNs (16.0 +/- 5% phagocytosis). In 7 h CLP rats, liver-sequestered PMNs exhibited a significantly higher level of superoxide anion generation 21.8 +/- 12.2 nmol/30 min/10(6) cells than did Kupffer cells (4.2 +/- 3.0 nmol/30 min/10(6) cells). These results demonstrate that the liver is a target organ for neutrophil sequestration during the septic response.(ABSTRACT TRUNCATED AT 250 WORDS)