Introduction CD14hi/CD16+ monocytes resemble tissue macrophages and normally constitute ∼5% of circulating monocytes. Expansion of CD14hi/CD16+ monocytes has been implicated in the perpetuation of liver injury and hepatic fibrosis in chronic liver disease. We therefore wanted to explore whether CD14hi/CD16+ monocytes are implicated in ALI; show features of activated endothelial adhesion (CD11b) and chemotaxis (CCR5); and phenotypically resemble classically activated “M1” or alternatively activated “M2” macrophages. “M1” macrophages secrete pro-inflammatory cytokines, express high levels of HLA-DR and CD86 and are implicated in tissue damage. “M2” macrophages, are immunoregulatory, express scavenger receptors such as CD163 and are involved in tissue repair.
Methods Blood was sampled from patients within 24–48 h of admission consisting of 33 hyper-Acute Liver Failure (hyperALF: jaundice to encephalopathy <7 days), 8 Subacute/Acute Liver Failure (S/ALF: jaundice to encephalopathy >7 days), and 18 healthy controls (HC). Flow cytometery was performed to investigate monocyte phenotype (CD14, CD16, HLA-DR, CD86, CD163, CD11b and CCR5).
Results Compared to HC, total monocyte count was elevated in S/ALF, but reduced in hyperALF (p<0.001), while CD14hi/CD16+ monocytes were expanded in percentage of total monocytes and absolute numbers in S/ALF (17.4%; 0.14) compared to HC (4%; 0.014) (p<0.001). Although the percentage of CD14hi/CD16+ monocytes in hyperALF was higher (5.6%, p<0.01), the absolute number (0.013) was similar to HC. Though all CD14hi/CD16+ monocytes expressed HLA-DR, the Mean Fluorescence Intensity (MFI) was reduced compared to HC (<0.001). HyperALF CD14hi/CD16+ monocytes had lower HLA-DR MFI compared to S/ALF (p<0.001). A similar pattern was seen for CD86 expression (p<0.01). CD14hi/CD16+ monocytes showed increased expression of CD163 in hyperALF but not in S/ALF compared to HC (<0.01). Compared to HC, CD11b and CCR5 were up-regulated in all ALF groups (p<0.001).
Conclusion We have demonstrated an expansion of CD14hi/CD16+ monocytes in ALI with an activated phenotype for adhesion and migration. CD14hi/CD16+ monocytes phenotypically resemble M1 macrophages in S\ALF, possibly reflecting a pathogenic role in the perpetuation of liver injury, while they resemble M2 in hyperALF and may be instrumental to the resolution of liver injury. This distinction requires further investigation should therapeutic strategies to target monocyte migration be attempted.
Competing interests None declared.