Complement receptor type three (CD11b/CD18) of human polymorphonuclear leukocytes recognizes fibrinogen

Area of Science:

• Immunology
• Cell Biology
• Biochemistry

Background:

• Human polymorphonuclear leukocytes (PMN) interact with fibrin and fibrinogen.
• PMN-fibrinogen interactions create a protected compartment for secreted elastase.
• Complement receptor type 3 (CR3) is known to bind the complement protein fragment C3bi.

Purpose of the Study:

• To identify the specific receptor on PMN responsible for binding to fibrinogen-coated surfaces.
• To investigate the role of CR3 in PMN-fibrinogen interactions and protected compartment formation.
• To determine the specific binding site on fibrinogen recognized by CR3.

Main Methods:

• Utilized monoclonal antibodies against CR3 to block C3bi binding.
• Assessed the effect of these antibodies on PMN binding to fibrinogen-coated surfaces.
• Employed peptides derived from the gamma chain of fibrinogen to inhibit PMN binding.
• Investigated the binding of C3bi-coated erythrocytes to CR3 using these peptides.
• Performed sequence analysis to compare fibrinogen-binding regions with known CR3 ligands.

Main Results:

• Monoclonal antibodies blocking C3bi binding also inhibited PMN binding to fibrinogen.
• CR3 mediates the interaction between PMN and fibrinogen-coated surfaces.
• A specific region at the carboxyl terminus of the fibrinogen gamma chain is recognized by CR3.
• The same binding site on CR3 is used for both C3bi and fibrinogen.
• Structural similarities exist between the fibrinogen-binding region and other CR3 ligands.

Conclusions:

• Complement receptor type 3 (CR3) functions as a direct receptor for fibrinogen on PMN.
• CR3 mediates PMN adhesion to fibrinogen, contributing to protected elastase activity.
• The findings reveal a dual role for CR3 in immune responses, binding both complement and matrix proteins.