Adsorbed fibrinogen regulates the behavior of human dendritic cells in a CD18-dependent manner.
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-1beta 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. Epsilon-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 beta(2) integrin-mediated interaction with dendritic cells.
Thacker
Robert I
RI
Department of Pathology and Laboratory Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267-0529, USA. thackeri@email.uc.edu
Retzinger
Gregory S
GS
D000327:Adsorption; D015119:Aminocaproic Acid / Q000494:pharmacology; D019138:Antibodies, Blocking / Q000494:pharmacology; D018821:CD18 Antigens / Q000276:immunology / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D005338:Fibrin Fibrinogen Degradation Products / Q000494:pharmacology; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding / Q000187:drug effects
D019138:Antibodies, Blocking; C111835:CCL2 protein, human; D018821:CD18 Antigens; D018932:Chemokine CCL2; D016207:Cytokines; D005338:Fibrin Fibrinogen Degradation Products; C015214:fibrinogen D fragment; D005340:Fibrinogen; D015119:Aminocaproic Acid