Abstract:Objective To explore the effect of macrophage phenotype transformation on the occurrence and development of systemic sclerosis. Methods 80 healthy BALB/c female mice were randomly divided into control group and systemic sclerosis model group, with 40 mice in each group. The control group was injected with normal saline 0.1 mL/(200 g·d) on the back, and the model group was injected with Bleomycin 0.1 mL/(200 g·d) on the back. Skin tissues were stained for hematoxylin and eosin(HE) to evaluate the disease progression, and flow cytometry was performed to detect the expression levels of scavenger receptor class B1 (SR-B1), scavenger receptor class A1(SR-A1) and Integrin beta 5 (ITGβ5), and RT-PCR for mRNA levels of macrophage polarizing factor inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1); ELISA for serum inflammatory factors Interleukin-17 (IL-17), Interleukin-6 (Interleukin-6), and Interleukin-6, Interleukin-6 (IL-6), Tumor necrosis factor alpha(TNF-α), Matrix metalloproteinase-9(MMP-9), Transforming growth factor beta-1(TGF-β1) and Growth arrest-specific 6 (GAS6), Milk fat globule-EGF factor 8 (MFG-E8) expression. Primary bone marrow-derived macrophages were extracted and the macrophage phagocytosis index (PI) was detected by flow cytometry. Results At the 7th, 14th, 21th and 28th day after injection, compared with the blank control group, hematoxylin and eosin (HE) staining showed that the thickness of the back epidermis in the model group was significantly increased(P<0.05), the skin appendages such as sebaceous glands and hair follicles in the model group were significantly reduced, and the fat layer was surrounded by fibrous tissue; compared with the blank control group, the expression of the M1 macrophages polarization marker iNOS in the model group was up-regulated, the expression of the M2 polarization marker Arg-1 was down-regulated. The expression of serum inflammatory factors such as IL-17, IL-6, TNF-α, MMP-9, and TGF-β was up-regulated (P<0.05); the expression of efferocytosis bridge molecules (GAS6 and MFG-E8) (P<0.05), scavenger receptors (SR-B1, SR-A1, and ITGβ5) and PI were down-regulated. Conclusion Macrophage phenotypic conversion to M1 type is positively correlated with decreased macrophage efferocytosis and may jointly contribute to the inflammatory response and disease progression in systemic sclerosis.