Functional Activation of the Formyl Peptide Receptor by a New Endogenous Ligand in Human Lung A549 Cells

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.

Identification of an essential endogenous regulator of blood–brain barrier integrity, and its pathological and therapeutic implications

“…Treatment of WT hCMEC/D3 cells for 3 h or 24 h with 20 μg/mL hrANXA1 induced a marked increase in intracellular ANXA1 (Fig. 6A), a result supported by previous studies identifying a similar effect of bioactive ANXA1 N-terminal peptide fragments upon total intracellular ANXA1 (20).…”

The G-protein-coupled formylpeptide receptor FPR confers a more invasive phenotype on human glioblastoma cells

“…Recently, a number of host-derived chemotactic agonists of FPR have been identified, including formylpeptides potentially released by mitochondria of ruptured cells (Rabiet et al, 2005), annexin I produced by activated epithelia (Xia et al, 2002) and a neutrophil granule protein, cathepsin G (Sun et al, 2004). In addition, functional FPR has been detected in cells of nonhaematopoietic origin, such as lung epithelial cells (Rescher et al, 2002) and hepatocytes (McCoy et al, 1995). These findings expanded the spectrum of pathophysiologic processes in which FPR may have a function.…”

Annexin I Regulates SKCO-15 Cell Invasion by Signaling through Formyl Peptide Receptors

“…Expression of nFPRs has been identified in some epithelial cell types including lung epithelia and hepatocytes (82,83). Immunohistochemical studies using rabbit polyclonal anti-FPR-1 antibodies suggest that it is also expressed in small intestinal epithelial cells (84).…”