Title: Serum amyloid A chemoattracts immature dendritic cells and indirectly provokes monocyte chemotaxis by induction of cooperating CC and CXC chemokines
Authors: Gouwy, Mieke * ×
De Buck, Mieke *
Pörtner, Noëmie
Opdenakker, Ghislain
Proost, Paul
Struyf, Sofie
Van Damme, Jozef #
Issue Date: Jan-2015
Publisher: Wiley-VCH
Series Title: European Journal of Immunology vol:45 pages:101-112
Article number: 10.1002/eji.201444818
Abstract: Serum amyloid A (SAA) is an acute phase protein that is upregulated in inflammatory diseases and chemoattracts monocytes, lymphocytes, and granulocytes via its G protein-coupled receptor formyl peptide receptor like 1/formyl peptide receptor 2 (FPRL1/FPR2). Here, we demonstrated that the SAA1α isoform also chemoattracts monocyte-derived immature dendritic cells (DCs) in the Boyden and μ-slide chemotaxis assay and that its chemotactic activity for monocytes and DCs was indirectly mediated via rapid chemokine induction. Indeed, SAA1 induced significant amounts (≥5 ng/mL) of macrophage inflammatory protein-1α/CC chemokine ligand 3 (MIP-1α/CCL3) and interleukin-8/CXC chemokine ligand 8 (IL-8/CXCL8) in monocytes and DCs in a dose-dependent manner within 3 h. However, SAA1 also directly activated monocytes and DCs for signaling and chemotaxis without chemokine interference. SAA1-induced monocyte migration was nevertheless significantly prevented (60-80% inhibition) in the constant presence of desensitizing exogenous MIP-1α/CCL3, neutralizing anti-MIP-1α/CCL3 antibody, or a combination of CC chemokine receptor 1 (CCR1) and CCR5 antagonists, indicating that this endogenously produced CC chemokine was indirectly contributing to SAA1-mediated chemotaxis. Further, anti-IL-8/CXCL8 antibody neutralized SAA1-induced monocyte migration, suggesting that endogenous IL-8/CXCL8 acted in concert with MIP-1α/CCL3. This explained why SAA1 failed to synergize with exogenously added MIP-1α/CCL3 or stromal cell-derived factor-1α (SDF-1α)/CXCL12 in monocyte and DC chemotaxis. In addition to direct leukocyte activation, SAA1 induces a chemotactic cascade mediated by expression of cooperating chemokines to prolong leukocyte recruitment to the inflammatory site.
ISSN: 0014-2980
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Molecular Immunology (Rega Institute)
Laboratory of Immunobiology (Rega Institute)
* (joint) first author
× corresponding author
# (joint) last author

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