Engagement of the monocyte surface antigen CD14 induces lymphocyte function-associated antigen-1/intercellular...

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• CD14 is a key receptor on monocytes involved in innate immunity.
• Monocyte adhesion is crucial for inflammatory responses and immune cell trafficking.
• Understanding CD14-mediated adhesion mechanisms can reveal new therapeutic targets.

Purpose of the Study:

• To investigate the mechanism by which anti-CD14 monoclonal antibodies (mAbs) induce monocyte homotypic adhesion.
• To identify the specific adhesion molecules and signaling pathways involved in CD14-dependent monocyte aggregation.

Main Methods:

• Utilized murine anti-CD14 mAbs to induce monocyte adhesion in vitro.
• Tested the requirement for divalent cations (Mg2+), temperature, and antibody fragment types (F(ab)'2, F(ab)).
• Assessed the role of various adhesion molecules (CD11a, CD11b, CD11c, CD18, ICAM-1) and protein kinase inhibitors (sphingosine).
• Examined cells from a patient with leukocyte adhesion deficiency.

Main Results:

• Anti-CD14 mAbs induced significant homotypic adhesion of normal human monocytes.
• This adhesion required Mg2+ and optimal temperature (37°C), and was mediated by lymphocyte function-associated antigen-1 (LFA-1)/intercellular adhesion molecule-1 (ICAM-1) interactions.
• Adhesion was independent of Fc gamma receptor engagement and CD14 cross-linking, and was blocked by sphingosine, indicating protein kinase involvement.
• Cells from a patient with leukocyte adhesion deficiency did not aggregate, confirming the role of LFA-1/ICAM-1.

Conclusions:

• CD14 engagement by specific mAbs induces monocyte adhesion through LFA-1/ICAM-1 pathway.
• Protein kinases are involved in the intracellular signaling coupling CD14 to LFA-1/ICAM-1-mediated adhesion.
• These findings elucidate a novel mechanism of CD14-dependent monocyte adhesion with potential implications for inflammatory diseases.