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Functional activation of the formyl peptide receptor by a new endogenous ligand in human lung A549 cells
Ursula Rescher1, Antje Danielczyk, Arseni Markoff
1Center for Molecular Biology of Inflammation, Institute for Medical Biochemistry, Münster, Germany.
Abstract:
The formyl peptide receptor (FPR), a heptahelical G protein-coupled receptor on phagocytic leukocytes, can be triggered by bacterially derived oligopeptides of the prototype fMLP. Although FPR expression and activation have been associated with cells of myeloid origin and bacterial inflammation, the receptor has recently been identified in nonmyeloid cells, thus suggesting additional physiological functions and the existence of an endogenous agonist. In this study, we demonstrate the presence and functional activation of the FPR in the human lung cell line A549, which represents an extrahepatic model for the regulation of acute-phase proteins. Activation of the FPR in A549 cells cannot only be triggered by fMLP, but also by an agonistic peptide of the recently identified endogenous FPR ligand, annexin 1. In addition to inducing changes in the F-actin content, annexin 1-mediated triggering of the FPR results in an increased expression of acute-phase proteins. Hence, activation of nonmyeloid FPR by its endogenous ligand annexin 1 could participate in the regulation of acute-phase responses, e.g., during inflammation and/or wound healing.
Insights
The formyl peptide receptor (FPR) is activated in human lung cells by annexin 1, an endogenous ligand. This activation influences acute-phase protein expression, suggesting a role in inflammation and wound healing.
Area of Science:
- Immunology
- Cell Biology
- G protein-coupled receptor signaling
Background:
- The formyl peptide receptor (FPR) is a G protein-coupled receptor typically found on phagocytic leukocytes.
- FPR activation by bacterial peptides like fMLP is linked to myeloid cells and bacterial inflammation.
- Recent findings show FPR in nonmyeloid cells, indicating broader functions and endogenous ligands.
Purpose of the Study:
- To investigate the presence and functional activation of FPR in the human lung cell line A549.
- To explore the role of the endogenous FPR ligand, annexin 1, in activating FPR in nonmyeloid cells.
- To determine the downstream effects of FPR activation in A549 cells, particularly concerning acute-phase protein expression.
Main Methods:
- Utilized the human lung cell line A549 as an extrahepatic model.
- Stimulated A549 cells with both fMLP and an annexin 1-derived peptide.
- Assessed changes in F-actin content and acute-phase protein expression following FPR activation.
Main Results:
- Demonstrated the presence and functional activation of FPR in A549 cells.
- Confirmed that both fMLP and annexin 1 can trigger FPR in these lung cells.
- Observed alterations in F-actin content and significantly increased expression of acute-phase proteins upon annexin 1-mediated FPR activation.
Conclusions:
- Nonmyeloid FPR, specifically in human lung cells, can be activated by the endogenous ligand annexin 1.
- Annexin 1-induced FPR activation in A549 cells leads to altered F-actin and increased acute-phase protein expression.
- This suggests a potential role for nonmyeloid FPR in regulating acute-phase responses during inflammation and wound healing.
