Macrophage polarization and macrophage-related factor expression in hypertrophy of the ligamentum flavum

Owing to the unknow types of infiltrating macrophages and the corresponded factors, we aimed to investigate the specific types of infiltrating macrophages involved in HLF and the expression of macrophage-related factors.

The ligamentum flavum was obtained from patients with lumbar spinal stenosis (HLF group; n = 15) and lumbar disc herniation (non-hypertrophic ligamentum flavum [NLF] group; n = 15). Ligamentum flavum specimens were paraffin embedded, followed by histological and immunohistochemical staining to identify the macrophage type and expression of macrophage-related factors.

The HLF group demonstrated CD206 marker expression, while the NLF group did not (P < 0.0001; n = 11). CD68 marker was expressed in both groups (P > 0.05; n = 11). CCR7 was not expressed in either group. The expression levels of the extracellular matrix proteins aggrecan (Agg), type I collagen (Coll1), and type II collagen (Coll2) were higher in the HLF group than in the NLF group (P < 0.0001; n = 11). The aging markers p21, p16, and p53 were expressed in the HLF group, but not in the NLF group (P < 0.0001; n = 11). The expression levels of the inflammatory factors TNF-α and IL-1β were higher in the HLF group than in the NLF group (P < 0.0001; n = 11). Similarly, the expression level of the fibrosis factor TGF-β1 was higher in the HLF group than in the NLF group (P < 0.0001; n = 11).

The infiltration of M2 macrophages may be involved in HLF, while involvement of M1 macrophages may only occur early in inflammation. The expression of extracellular matrix proteins and macrophage-related factors was increased. Aging may also be associated with HLF.