Splenectomy Promotes Macrophage Polarization in a Mouse Model of Concanavalin A- (ConA-)‎ Induced Liver Fibrosis

Abstract EN

Background.

Splenectomy can improve liver function and survival in patients with autoimmune hepatitis (AIH) and liver cirrhosis.

We investigated the underlying mechanism in a mouse model of concanavalin A- (ConA-) induced liver fibrosis.

Methods.

We used ConA to induce immune liver fibrosis in BALB/c mice.

Splenectomy was performed alone or with the administration of dexamethasone (DEX).

Changes in blood and liver tissues were evaluated.

Results.

Mice treated with ConA for 7 weeks developed advanced liver fibrosis, while splenectomy suppressed liver fibrosis.

Although the populations of macrophages/monocytes and M1 macrophages decreased after splenectomy, the inflammatory factors associated with M2 macrophages increased after splenectomy.

Furthermore, the population of circulating CD11b+Ly6Chigh myeloid-derived suppressor cells (MDSCs) increased after splenectomy.

After ConA treatment, elevated levels of activated and total NF-kBp65/p50 combined with DNA were observed in hepatic tissues.

In contrast, the levels of NF-κB p65/p50 decreased after splenectomy.

Conclusions.

Splenectomy may promote the polarization of CD11b+Ly6Chigh MDSCs and the differentiation of M2 macrophages while restricting the level of NF-κB p65-p50 heterodimers.

These factors may suppress the progression of liver fibrosis.