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Beta 2-integrin-mediated signal up-regulates counterreceptor ICAM-1 expression on human monocytic cell line THP-1

A Yamada1, A Hara, M Inoue

  • 1Department of Immunology, Kurume University School of Medicine, Japan.

Cellular Immunology
|May 25, 1997
PubMed

Insights

Stimulating LFA-1 (leukocyte function-associated antigen 1) with specific antibodies increases ICAM-1 (intercellular adhesion molecule-1) expression on THP-1 cells. This upregulation involves tyrosine phosphorylation, suggesting a key signaling pathway.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Intercellular adhesion molecule-1 (ICAM-1) plays a crucial role in immune cell interactions.
  • LFA-1 (leukocyte function-associated antigen 1) is a key integrin involved in cell adhesion and immune responses.
  • Understanding the cross-talk between LFA-1 and ICAM-1 is vital for deciphering immune cell signaling.

Purpose of the Study:

  • To investigate the intracellular signaling pathways mediating the upregulation of ICAM-1 expression by LFA-1 stimulation.
  • To analyze the cross-talk between LFA-1 and ICAM-1 in human monocytic THP-1 cells.

Main Methods:

  • THP-1 cells were stimulated with specific monoclonal antibodies (mAbs) targeting LFA-1 subunits (CD11a, CD11b, CD18) and beta 1-integrin.
  • Cell surface ICAM-1 expression was quantified using flow cytometry.
  • mRNA levels of ICAM-1 were analyzed by Northern blotting.
  • The effect of tyrosine kinase inhibitors (herbimycin A, genistein) on ICAM-1 upregulation was assessed.

Main Results:

  • Stimulation with anti-LFA-1 alpha (CD11a) mAb YH384 dose-dependently upregulated ICAM-1 surface expression and mRNA levels in THP-1 cells.
  • Maximum ICAM-1 expression was observed 24 hours post-stimulation, with maximal mRNA levels at 4 hours.
  • Upregulation was specific to ICAM-1, with no significant changes in nine other tested molecules.
  • Antibodies targeting other beta 2-integrin family members (CD11a, CD11b, CD18) also upregulated ICAM-1, while anti-beta 1-integrin mAb showed a weaker effect.
  • Tyrosine kinase inhibitors herbimycin A and genistein suppressed the YH384-induced ICAM-1 upregulation.

Conclusions:

  • Beta 2-integrin-mediated upregulation of ICAM-1 expression is dependent on tyrosine phosphorylation.
  • These findings elucidate a critical signaling pathway involved in LFA-1/ICAM-1 interactions within monocytic cells.
  • This pathway may represent a therapeutic target for modulating immune cell adhesion and inflammatory responses.

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