Abstract
C5L2 is an enigmatic serpentine receptor that is co-expressed with the C5a receptor on many cells including polymorphonuclear neutrophils. The apparent absence of coupling of C5L2 with G proteins suggests that this receptor may modulate the biological activity of C5a, perhaps by acting as a decoy receptor. Alternatively, C5L2 may affect C5a function through formation of a heteromeric complex with the C5aR, or it may utilize a G protein-independent signaling pathway. Here we show that in mice bearing a targeted deletion of C5L2, the biological activity of C5a/C5a(desArg) is enhanced both in vivo and in vitro. The biological role of C5L2 thus appears to be limiting to the pro-inflammatory response to the anaphylatoxin. Accordingly, up-regulation of C5L2 may be of benefit in inflammatory states driven by C5a, including sepsis, asthma, cystic fibrosis, and chronic obstructive lung disease.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Anaphylatoxins / chemistry
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Animals
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Anti-Inflammatory Agents / pharmacology*
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Bone Marrow Cells / metabolism
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Chemotaxis
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Cloning, Molecular
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Complement C5a / chemistry*
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DNA, Complementary / metabolism
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Female
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GTP-Binding Proteins / metabolism
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Gene Expression Regulation
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Inflammation
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Interleukin-6 / biosynthesis
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Lung / pathology
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Lung Injury
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Models, Genetic
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Neutrophils / metabolism
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Phenotype
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Protein Binding
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RNA, Messenger / metabolism
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Receptor, Anaphylatoxin C5a
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Receptors, Chemokine / genetics
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Receptors, Chemokine / physiology*
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Recombinant Proteins / chemistry
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Tumor Necrosis Factor-alpha / biosynthesis
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Up-Regulation
Substances
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Anaphylatoxins
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Anti-Inflammatory Agents
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C5ar2 protein, mouse
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DNA, Complementary
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Interleukin-6
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RNA, Messenger
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Receptor, Anaphylatoxin C5a
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Receptors, Chemokine
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Recombinant Proteins
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Tumor Necrosis Factor-alpha
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Complement C5a
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GTP-Binding Proteins