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Muscle, myeloid cells, and complement: a complex interaction

Cellular & Molecular Immunology volume 15, pages 992–993 (2018)Cite this article

The complement system is a critical arm of the immune system that plays an important role not only in maintaining health but also contributes to disease. Complement activation generates biologically active products C3a and C5a, which are important links between complement and cellular immunity. Recent studies have revealed that C5a/C5aR signaling is critical in both humoral and inflammatory responses, resulting in functional renal insufficiency in immune complex-mediated glomerulonephritis.1 Consistent with these studies and considering the complexity of complement system interactions based on location and setting, a recent article by Zhang et al.2 has shed light on C3a/C3aR signaling as the link that regulates monocyte function and trafficking and facilitates skeletal muscle regeneration. This commentary highlights the important themes originating from the work described, which include the following: (1) complement C3 depletion reduced muscle regeneration, (2) C3a signaling through its G-coupled receptor C3aR facilitated muscle regeneration by regulating monocyte/macrophage infiltration through CCL5, and (3) C5a/C5aR signaling does not affect monocyte/macrophage infiltration in this particular setting.

The complement cascade consists of three pathways that are initiated differently but ultimately form C5b-9, or the membrane attack complex. The pathways consist of approximately 30 proteins, both circulating and membrane bound, with regulators at strategic locations.3 Although complement remained unexplored for a long time after its discovery, different relevant proteins have been identified over time. More recently, complement research has become a dynamic area of study with discoveries of novel functions, and there is an urgency to identify effective complement therapies. Together with its traditionally understood role in immune defense,4 studies have revealed that complement plays an important role in differentiation, development, and disease.5, 6 The complement system is ubiquitous in the body, and its function is oriented towards the local microenvironment. In addition, too much or too little complement activation can be detrimental. Therefore, understanding its role in different organs and settings is important for enhancing health and in disease therapy.

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  1. Department of Medicine, SUNY at Buffalo, Buffalo, NY, 14086, USA

    Jessy J. Alexander & Richard J. Quigg

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Alexander, J.J., Quigg, R.J. Muscle, myeloid cells, and complement: a complex interaction. Cell Mol Immunol 15, 992–993 (2018). https://doi.org/10.1038/s41423-018-0049-4

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