Lysophosphatidic acid accelerates the development of human mast cells
| Autor: | Kursteen S. Price, Daniel S. Friend, Debbie A Lin, K. Frank Austen, Joshua A. Boyce, Savita Bagga |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Immunology Stem cell factor Apoptosis Biology Pertussis toxin Biochemistry Umbilical Cord chemistry.chemical_compound Internal medicine Lysophosphatidic acid medicine Humans Mast Cells RNA Messenger Receptors Lysophosphatidic Acid Receptor DNA Primers Base Sequence Growth factor Infant Newborn Cell Biology Hematology Mast cell Fetal Blood Cell biology Endocrinology medicine.anatomical_structure chemistry Cell culture Leukocytes Mononuclear lipids (amino acids peptides and proteins) Lysophospholipids Histamine Cell Division |
| Zdroj: | Blood. 104(13) |
| ISSN: | 0006-4971 |
| Popis: | Mast cells (MCs) initiate immune responses from mucosal surfaces and perivascular spaces. Stem cell factor (SCF) regulates MC development and viability, but the role of innate serum factors in MC development is unexplored. Cultured cord blood-derived human MCs (hMCs) express mRNA transcripts for all 4 known receptors for lysophosphatidic acid (LPA), an abundant serum-associated lipid growth factor. In an SCF-dependent serum-free culture system, LPA (2.5-10 μM) increased the total number of hMCs by approximately 10-fold compared with cultures maintained in the absence of LPA under otherwise identical conditions. LPA was comitogenic with SCF but did not prolong MC survival. LPA-mediated proliferation was blocked by VPC-32179, a competitive antagonist of LPA1 and LPA3 receptors, and by pertussis toxin, and it was also attenuated by GW9662, a selective antagonist of peroxisome proliferator-activated receptor (PPAR)-γ. LPA accelerated the acquisition of hMC granules and increased Kit expression. hMCs derived in the presence of LPA were functional, as evidenced by their immunoglobulin E (IgE)-dependent histamine release and by their characteristic proliferative responses to interleukin-3 (IL-3), IL-4, and IL-9 in combination with SCF. Thus, LPA acts through LPA receptor and PPAR-γ-dependent pathways to accelerate hMC proliferation and differentiation, and it modulates their phenotype without providing cytoprotection. LPA could facilitate MC hyperplasia in inflammation associated with either innate or adaptive immunity. (Blood. 2004; 104:4080-4087) |
| Databáze: | OpenAIRE |
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