Functional activation of the formyl peptide receptor by a new endogenous ligand in human lung A549 cells.
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.
Center for Molecular Biology of Inflammation, Institute for Medical Biochemistry, Münster, Germany.
Ursula
U
Rescher
Antje
A
Danielczyk
Arseni
A
Markoff
Volker
V
Gerke
D000199:Actins / Q000378:metabolism; D000210:Acute-Phase Reaction; D017305:Annexin A1 / Q000502:physiology*; D002478:Cells, Cultured; D005340:Fibrinogen / Q000096:biosynthesis; D006801:Humans; D008168:Lung / Q000737:chemistry; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000032:analysis / Q000502:physiology*; D018000:Receptors, Peptide / Q000032:analysis / Q000502:physiology*
D000199:Actins; D017305:Annexin A1; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D005340:Fibrinogen