ICAM-1 (CD54): a counter-receptor for Mac-1 (CD11b/CD18)

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• The interaction between leukocyte integrins and adhesion molecules is vital for immune cell trafficking.
• While lymphocyte function-associated antigen (LFA)-1 binding to intercellular adhesion molecule (ICAM)-1 is established, Mac-1's interaction with ICAM-1 remains controversial.
• Understanding these interactions is key to elucidating inflammatory and immune responses.

Purpose of the Study:

• To investigate and clarify the controversial interaction between the Mac-1 integrin and ICAM-1.
• To determine if ICAM-1 serves as a counter-receptor for Mac-1.
• To assess the role of the Mac-1/ICAM-1 interaction in neutrophil-endothelial cell adhesion.

Main Methods:

• Utilized multiple cell binding assays with purified Mac-1, ICAM-1, and transfected cell lines.
• Employed immunoaffinity purification of Mac-1 and ICAM-1.
• Conducted reciprocal binding assays and two-color fluorescence cell conjugate experiments.

Main Results:

• Stimulated endothelial cells expressing ICAM-1 bound to purified Mac-1, an interaction inhibited by antibodies to Mac-1 and ICAM-1.
• Transfected cells expressing ICAM-1 showed specific, dose-dependent binding to Mac-1, distinct from LFA-1 binding characteristics.
• Neutrophil binding to endothelial cells was dependent on ICAM-1, Mac-1, and LFA-1.

Conclusions:

• Intercellular adhesion molecule (ICAM)-1 is confirmed as a counter-receptor for the Mac-1 integrin.
• The Mac-1/ICAM-1 receptor pair contributes to the adhesion between stimulated neutrophils and endothelial cells.
• This finding resolves controversy and clarifies a significant mechanism in leukocyte adhesion.