The interaction between C5a and both C5aR and C5L2 receptors is required for production of G-CSF during acute inflammation. 2013

Markus Bosmann, and Mikel D Haggadone, and Firas S Zetoune, and J Vidya Sarma, and Peter A Ward
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-5602, USA.

The complement activation product, C5a, is a key factor for regulation of inflammatory responses. C5a and C5adesArg bind to their receptors, C5aR and C5L2, but the functional roles of C5L2 remain controversial. We screened the patterns of 23 inflammatory mediators in cultures of LPS-activated mouse peritoneal elicited macrophages (PEMs) in the presence or absence of recombinant mouse C5a. Production of most mediators studied was suppressed by C5a, whereas G-CSF production was enhanced. G-CSF gene expression and secretion from PEMs was amplified two- to threefold by C5a in a dose- and time-dependent fashion. The degradation product C5adesArg promoted lower levels of G-CSF. The effects of C5a on G-CSF were associated with activation of PI3K/Akt and MEK1/2 signaling pathways. C5a did not enhance G-CSF production in cultures of PEMs from either C5aR- or C5L2-deficient mice, indicating that both C5a receptors are indispensable for mediating the effects of C5a in the production of G-CSF. Finally, G-CSF levels in plasma during polymicrobial sepsis after cecal ligation and puncture were substantially lower in C5aR- or C5L2-deficient mice as compared with that in C57BL/6J WT mice. These findings elucidate the functional characteristics of the C5L2 receptor during the acute inflammatory response.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D011951 Receptors, Complement Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement. Complement Receptors,Complement Receptor,Complement Receptor Type 1,Receptor, Complement
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004797 Enzyme-Linked Immunosorbent Assay An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked
D000208 Acute Disease Disease having a short and relatively severe course. Acute Diseases,Disease, Acute,Diseases, Acute
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015936 Complement C5a The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION. C5a Complement,Complement 5a,Complement Component 5a,C5a, Complement,Complement, C5a,Component 5a, Complement
D016179 Granulocyte Colony-Stimulating Factor A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. Colony-Stimulating Factor, Granulocyte,G-CSF,Myeloid Growth Factor,Colony Stimulating Factor, Granulocyte,Factor, Granulocyte Colony-Stimulating,Factor, Myeloid Growth,Granulocyte Colony Stimulating Factor,Growth Factor, Myeloid

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