Multiple signalling pathways in the C5a-induced expression of adhesion receptor Mac-1

Area of Science:

• Immunology
• Cell Biology
• Molecular Signaling

Background:

• The CD11/CD18 leukocyte glycoprotein family mediates cell adhesion during acute inflammation.
• Mac-1 (CD11b/CD18) expression on monocytes and neutrophils increases with inflammatory stimuli.
• Intracellular signaling pathways controlling Mac-1 upregulation remain incompletely understood.

Purpose of the Study:

• To investigate the roles of G proteins and extracellular calcium (Ca2+) in Mac-1 upregulation.
• To elucidate signaling mechanisms stimulated by the chemoattractant C5a in U937 cells.

Main Methods:

• Utilized the human monocyte-like cell line U937.
• Examined the effects of the chemoattractant C5a on Mac-1 expression.
• Assessed the involvement of G proteins (using pertussis toxin) and extracellular Ca2+ influx.

Main Results:

• Identified two distinct signal transduction pathways involved in Mac-1 upregulation.
• Demonstrated that a pertussis toxin-insensitive extracellular Ca2+ influx contributes to Mac-1 upregulation in U937 cells.
• Highlighted a difference compared to neutrophils, where chemotactic peptide-induced Mac-1 upregulation is pertussis toxin-sensitive and Ca2+-independent.

Conclusions:

• Extracellular Ca2+ influx is a significant component of the signaling network leading to Mac-1 upregulation in U937 cells.
• The signaling pathway for Mac-1 upregulation in U937 cells differs from that observed in neutrophils.
• Further research is needed to fully delineate the complex intracellular signaling mechanisms controlling leukocyte adhesion molecule expression.