Interleukin-18 Amplifies Macrophage Polarization and Morphological Alteration, Leading to Excessive Angiogenesis

Area of Science:

• Immunology
• Cell Biology
• Angiogenesis Research

Background:

• M2 macrophages (Mφ) drive pathologic angiogenesis in inflammatory diseases like rheumatoid arthritis and cancer.
• Interleukin-18 (IL-18) is implicated in excessive angiogenesis, but the precise mechanism involving M2 Mφs is unclear.

Purpose of the Study:

• To investigate the mechanism by which M2 Mφs, in an IL-18-containing environment, induce excessive angiogenesis.
• To elucidate the molecular interactions between M2 Mφs and endothelial cells.

Main Methods:

• Utilized an in vitro experimental model with mouse Mφ-like RAW264.7 cells and mouse endothelial b.End5 cells.
• Analyzed the synergistic effects of IL-18 and IL-10 on Mφ-derived mediator production.
• Visualized temporal and morphological changes of Mφs during angiogenesis.

Main Results:

• IL-18 synergizes with IL-10 to enhance Mφ production of osteopontin (OPN) and thrombin.
• Thrombin-cleaved OPN generation, acting via integrins α4/α9, augments M2 polarization and CD163 expression.
• M2-like Mφs induced excessive angiogenesis through direct cell-cell interaction with endothelial cells, possibly mediated by CD163.

Conclusions:

• IL-18 and IL-10 collaboratively promote M2 macrophage-driven angiogenesis via enhanced mediator production and direct cell interactions.
• CD163 may play a crucial role in mediating the pro-angiogenic interactions between M2 macrophages and endothelial cells.