Hepatic macrophages promote the neutrophil-dependent resolution of fibrosis in repairing cholestatic rat livers

Neutrophil Depletion Blocks Early Collagen Degradation in Repairing Cholestatic Rat Livers

“…All animals exhibited obstruction as evidenced by bile duct dilatation, expected weight loss, and hyperbilirubinemia. 13,14 In the 2-day repair group, 4 rats (of the 21 studied) did not demonstrate bile duct decompression grossly by clearing of jaundice and persistent ductal dilatation. They were excluded from the study.…”

“…KC depletion in conjunction with a reduction in the number of PMNs in the liver, however, was sufficient to inhibit fibrotic degradation. Moreover, we have also shown that fibrosis resolution, following biliary decompression, is concurrent with a increase in matrix metalloproteinase (MMP)8 expression and activity 13,14 without a contribution from the other main collagenase, MMP13 identified in rat liver. These findings may suggest a more meaningful effector role for PMNs and MMP8 in the resorption of matrix compared with KCs and MMP 13 during repair.…”

“…5,13,15 The peri-portal region is a prominent location of matrix deposition during injury and collagen resorption during repair. Our results reveal that unlike KC and recruited macrophage clearance from the liver after biliary decompression, PMNs persist after decompression and remain elevated during repair.…”

80. Dexamethasone Alters the Hepatic Inflammatory Cellular Profile Without Changes in Matrix Degradation During Liver Repair Following Biliary Decompression

“…Our previous results demonstrate that there is an increase in neutrophil numbers into the portal regions in response to bile duct obstructive cholestatic injury. (15,16) This neutrophil response is persistent following biliary decompression and restoration of bile flow and we hypothesize is the basis for the neutrophildependant repair observed in our model. (16) It is interesting to note that despite the dexamethasone-induced reduction in macrophage and Kupffer cells, the hepatic gene expression of the neutrophil chemoattractant CINC-1 was not significantly changed in the steroid treated rats.…”

DHRS3, a retinal reductase, is differentially regulated by retinoic acid and lipopolysaccharide-induced inflammation in THP-1 cells and rat liver

“…3D, image c), which has been reported by us (32) and others (37) to have a strong expression and hepatocyte-exclusive distribution. As a nonparenchymal cell-specific gene, we used CXCL1, which has been reported to be expressed in neutrophils and Kupffer cells in response to liver injury (16). We found no signal for CXCL1 in the section of the liver of normal rats (data not shown), but in the liver of rats treated with LPS, CXCL1 was detected in isolated cells or small clusters appearing as mononuclear cells (Fig.…”