Expression and function of formyl peptide receptors on human fibroblast cells.
The migration of polymorphonuclear leukocytes from the blood to sites of infection in tissues is a hallmark of the innate immune response. Formylated peptides produced as a byproduct of bacterial protein synthesis are powerful chemoattractants for leukocytes. Formyl peptides bind to two different G protein-coupled receptors (formyl peptide receptor (FPR) and the low affinity formyl peptide receptor-like-1 (FPRL1)) to initiate a signal transduction cascade leading to cell activation and migration. Our analysis of expressed sequences from many cDNA libraries draws attention to the fact that FPRs are widely expressed in nonlymphoid tissues. Here we demonstrate that FPRs are expressed by normal human lung and skin fibroblasts and the human fibrosarcoma cell line HT-1080. The expression on fibroblasts of receptors for bacteria-derived peptides raises questions about the possible function of these receptors in nonleukocyte cells. We studied the function of FPRs on fibroblasts and find that stimulation with fMLP triggers dose-dependent migration of these cells. Furthermore, fMLP induces signal transduction including intracellular calcium flux and a transient increase in F-actin. The fMLP-induced adhesion and motility of fibroblasts on fibronectin require functional protein kinase C and phosphatidylinositol 3-kinase. This first report of a functional formyl peptide receptor in cells of fibroblast origin opens new possibilities for the role of fibroblasts in innate immune responses.
VanCompernolle
Scott E
SE
Program in Molecular Cellular and Developmental Biology, Division of Biology, Kansas State University, Manhattan, KS 66506, USA.
Clark
Krista L
KL
Rummel
Kevin A
KA
Todd
Scott C
SC
D000199:Actins / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D007113:Immunity, Innate; D007424:Intracellular Fluid / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism* / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology*; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000199:Actins; D000276:Adjuvants, Immunologic; C105101:FPR2 protein, human; D005353:Fibronectins; D011956:Receptors, Cell Surface; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D037342:Pertussis Toxin; D002118:Calcium