Adsorbed fibrinogen regulates the behavior of human dendritic cells in a CD18-dependent manner

Robert I. Thacker, Gregory S. Retzinger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

The involvement of fibrinogen in inflammation has been considered by many, but the roles of the protein in that process have yet to be fully elucidated. The protein readily coats surfaces and is deposited at sites of inflammation. Furthermore, adsorbed fibrinogen influences many cells of the immune system, likely a result of increased receptor recognition upon ligand immobilization. To better understand adsorbed fibrinogen's role in inflammation, we studied the effects of the protein, adsorbed to the surface of microscopic beads, on human dendritic cells. Adsorbed fibrinogen increased dendritic cell expression of IL-6, IL-8, MIP-1β and MCP-1. In contrast, solution phase fibrinogen had no effect. Importantly, dendritic cells formed complexes with, and subsequently accumulated around, beads in fibrinogen-dependent fashion. Antibodies directed against CD18 significantly decreased cytokine/chemokine expression and bead-cell complexation. e{open}-aminocaproic acid limited bead-cell complexation, suggesting fibrinogen degradation products modulate dendritic cell activity. In support of this proposal, fibrinogen fragment D also increased MCP-1 expression by human dendritic cells. Taken together our data indicate adsorbed fibrinogen and its degradation products directly influence human dendritic cell operation. We propose a model whereby adsorbed fibrinogen plays a distinct causatory role in inflammation through its β2 integrin-mediated interaction with dendritic cells.

Original languageEnglish (US)
Pages (from-to)122-130
Number of pages9
JournalExperimental and Molecular Pathology
Volume84
Issue number2
DOIs
StatePublished - Apr 1 2008

Keywords

  • Adhesion molecules
  • Cell activation
  • Chemokines
  • Chemotaxis
  • Cytokines
  • Dendritic cells
  • Fibrinogen
  • Inflammation
  • Integrins
  • Surfaces

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Pathology and Forensic Medicine

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