Absence of the P2X7 Receptor Alters Leukocyte Function and Attenuates an Inflammatory Response
| Autor: | Mary M. Payette, Laurent P. Audoly, Joan R. Wicks, William H. Brissette, Sandra P. McCurdy, Christopher A. Gabel, Carol Donovan, Nina Petrushova, Jeffrey M. Labasi, Paul D. Lira |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Lipopolysaccharides
Male medicine.medical_specialty T-Lymphocytes medicine.medical_treatment Immunology Arthritis Monocytes Leukocyte Count Mice Adenosine Triphosphate In vivo Internal medicine medicine Extracellular Animals Immunology and Allergy L-Selectin Receptor Collagen Type II Cells Cultured Inflammation Mice Knockout B-Lymphocytes biology Receptors Purinergic P2 Antibodies Monoclonal medicine.disease Arthritis Experimental Mice Inbred C57BL Cytokine Endocrinology Proteoglycan Mice Inbred DBA Monoclonal Leukocytes Mononuclear Macrophages Peritoneal biology.protein Female Receptors Purinergic P2X7 Antibody Injections Intraperitoneal Interleukin-1 |
| Zdroj: | The Journal of Immunology. 168:6436-6445 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | When challenged with extracellular ATP, leukocytes respond and activate processes attributed to the P2X7 receptor (P2X7R), an unusual ligand-gated ion channel. To prove P2X7R involvement, blood samples from P2X7R-deficient mice were characterized. Monocytes and lymphocytes associated with wild-type blood responded to ATP and underwent volume/shape changes and shed L-selectin. In contrast, leukocytes from P2X7R-deficient animals demonstrated no change in physical properties or L-selectin expression following ATP challenge. Blood stimulated with LPS or ATP individually generated minimal quantities of the leaderless polypeptide IL-1β, but sequential treatment of wild-type, but not P2X7R-deficient, blood with LPS and ATP yielded large amounts of cell-free cytokine. Based on these differences, wild-type and P2X7R-deficient animals were compared following induction of monoclonal anti-collagen-induced arthritis. Ab-treated wild-type animals subsequently challenged with LPS developed inflamed, swollen paws; their joint cartilage demonstrated lesions, loss of proteoglycan content, and the presence of collagen degradation products. P2X7R-deficient animals subjected to the same challenge were markedly less affected; both the incidence and severity of disease were reduced. These data indicate that ATP does act via the P2X7R to affect leukocyte function and that the P2X7R can serve as an important component of an in vivo inflammatory response. |
| Databáze: | OpenAIRE |
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