Histone H2B as a functionally important plasminogen receptor on macrophages

Area of Science:

• Immunology
• Cell Biology
• Biochemistry

Background:

• Plasminogen (Plg) binding to plasminogen receptors (Plg-Rs) is crucial for inflammatory cell recruitment.
• The specific Plg-Rs involved in macrophage migration remain incompletely understood.

Purpose of the Study:

• To investigate the contribution of four Plg-Rs (alpha-enolase, annexin 2, p11, and histone H2B [H2B]) to Plg binding and function on macrophages.
• To determine the critical role of H2B in Plg-mediated macrophage recruitment and inflammatory responses.

Main Methods:

• Analysis of Plg-R expression on murine macrophage cell lines and primary macrophages.
• Utilized blocking Fab fragments to quantify the contribution of individual Plg-Rs to Plg binding.
• Assessed the impact of anti-H2B Fab on plasmin generation, matrix invasion, and in vivo macrophage recruitment.

Main Results:

• All four Plg-Rs were detected on macrophages, with enhanced expression on thioglycollate-induced cells.
• Histone H2B (H2B) accounted for approximately 50% of Plg binding capacity, significantly more than other tested Plg-Rs.
• Blocking H2B function reduced plasmin generation, matrix invasion, and peritoneal macrophage recruitment by about 45% in vivo.

Conclusions:

• Multiple Plg-Rs contribute to Plg binding on macrophages.
• Histone H2B (H2B) plays a prominent and functionally critical role in Plg binding, plasmin generation, and inflammatory macrophage recruitment.