C1q as an autocrine and paracrine regulator of cellular functions
| Autor: | Berhane Ghebrehiwet, Ellinor I.B. Peerschke, Kinga K. Hosszu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Chemokine biology Complement C1q Immunology Antigen presentation Regulator Dendritic Cells Article Cell biology Immune tolerance Complement system Autocrine Communication 03 medical and health sciences Paracrine signalling 030104 developmental biology Paracrine Communication Immune Tolerance biology.protein Animals Humans Antigen-presenting cell Autocrine signalling Molecular Biology |
| Zdroj: | Molecular Immunology. 84:26-33 |
| ISSN: | 0161-5890 |
| Popis: | Most of the complement proteins in circulation are, by and large, synthesized in the liver. However data accumulated over the past several decades provide incontrovertible evidence that some if not most of the individual complement proteins are also synthesized extrahepatically by activated as well as non-activated cells. The question that is finally being addressed by various investigators is: are the locally synthesized proteins solely responsible for the myriad of biological functions in situ without the contribution of systemic complement? The answer is probably "yes". Among the proteins that are synthesized locally, C1q takes center stage for several reasons. First, it is synthesized predominantly by potent antigen presenting cells such as monocytes, macrophages and dendritic cells (DCs), which by itself is a clue that it plays an important role in antigen presentation and/or DC maturation. Second, it is transiently anchored on the cell surface via a transmembrane domain located in its A chain before it is cleaved off and released into the pericellular milieu. The membrane-associated C1q in turn, is able to sense danger patterns via its versatile antigen-capturing globular head domains. More importantly, locally synthesized C1q has been shown to induce a plethora of biological functions through the induction of immunomodulatory molecules by an autocrine- or paracrine- mediated signaling in a manner that mimics those of TNFα. These include recognition of pathogen- and danger- associated molecular patterns, phagocytosis, angiogenesis, apoptosis and induction of cytokines or chemokines that are important in modulating the inflammatory response. The functional convergence between C1q and TNFα in turn is attributed to their shared genetic ancestry. In this paper, we will infer to the aforementioned "local-synthesis-for-local function" paradigm using as an example, the role played by locally synthesized C1q in autoimmunity in general and in systemic lupus erythematosus in particular. |
| Databáze: | OpenAIRE |
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