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Expression and function of formyl peptide receptors on human fibroblast cells

Scott E VanCompernolle1, Krista L Clark, Kevin A Rummel

  • 1Program in Molecular Cellular and Developmental Biology, Division of Biology, Kansas State University, Manhattan, KS 66506, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|August 7, 2003
PubMed

Insights

Formyl peptide receptors (FPRs) are expressed by human fibroblasts, enabling these cells to migrate towards bacterial peptides. This discovery reveals a novel role for fibroblasts in the innate immune response.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Polymorphonuclear leukocyte migration to infection sites is key to innate immunity.
  • Formylated peptides from bacteria attract leukocytes via G protein-coupled receptors (FPRs and FPRL1).
  • FPRs are known to be widely expressed in non-lymphoid tissues.

Purpose of the Study:

  • To investigate the expression and function of formyl peptide receptors (FPRs) in non-leukocyte cells, specifically fibroblasts.
  • To determine if fibroblasts express FPRs and respond to bacterial chemoattractants.
  • To elucidate the signaling pathways involved in fibroblast response to formylated peptides.

Main Methods:

  • Analysis of expressed sequence data from cDNA libraries.
  • Demonstration of FPR expression in normal human lung and skin fibroblasts and HT-1080 fibrosarcoma cells.
  • Functional assays including cell migration, intracellular calcium flux, F-actin polymerization, and adhesion studies.
  • Investigating the role of protein kinase C and phosphatidylinositol 3-kinase in fMLP-induced fibroblast responses.

Main Results:

  • Formyl peptide receptors (FPRs) are expressed by human lung and skin fibroblasts and HT-1080 cells.
  • Stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP) induces dose-dependent migration of fibroblasts.
  • fMLP triggers intracellular calcium flux and F-actin increase in fibroblasts.
  • Fibroblast adhesion and motility on fibronectin in response to fMLP depend on protein kinase C and phosphatidylinositol 3-kinase.

Conclusions:

  • This study demonstrates functional formyl peptide receptors in fibroblasts for the first time.
  • Fibroblasts can migrate and exhibit signal transduction in response to bacterial chemoattractants.
  • These findings suggest a novel role for fibroblasts in innate immune responses, extending beyond their traditional functions.

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