Abstract
Macrophages are key players in various inflammatory disorders and pathological conditions via phagocytosis and orchestrating immune responses. They are highly heterogeneous in terms of their phenotypes and functions by adaptation to different organs and tissue environments. Upon damage or infection, monocytes are rapidly recruited to tissues and differentiate into macrophages. Transglutaminases (TGs) are a family of structurally and functionally related enzymes with Ca2+-dependent transamidation and deamidation activity. Numerous studies have shown that TGs, particularly TG2 and Factor XIII-A, are extensively involved in monocyte- and macrophage-mediated physiological and pathological processes. In the present review, we outline the current knowledge of the role of TGs in the adhesion and extravasation of monocytes, the expression of TGs during macrophage differentiation, and the regulation of TG2 expression by various pro- and anti-inflammatory mediators in macrophages. Furthermore, we summarize the role of TGs in macrophage phagocytosis and the understanding of the mechanisms involved. Finally, we review the roles of TGs in tissue-specific macrophages, including monocytes/macrophages in vasculature, alveolar and interstitial macrophages in lung, microglia and infiltrated monocytes/macrophages in central nervous system, and osteoclasts in bone. Based on the studies in this review, we conclude that monocyte- and macrophage-derived TGs are involved in inflammatory processes in these organs. However, more in vivo studies and clinical studies during different stages of these processes are required to determine the accurate roles of TGs, their substrates, and the mechanisms-of-action.
Highlights
Macrophages, which mean “big eaters” in Greek, are immune cells present in almost all tissues of the body with distinct tissue-specific phenotypes and functions
TG2, FXIII-A, and TG1 are all present in macrophages and their expressions are upregulated during macrophage differentiation
Studies showed that pro-inflammatory LPS and IFN-γ induced secretion of thioredoxin-1 (TRX) by macrophages was able to activate the extracellular TG2 in macrophages in vitro and that intravenous administration of TRX resulted in a rapid increase in TG2 activity exclusively in the small intestine in mice, suggesting that enhanced TG2 activity may be caused by inflammation in celiac disease [163]
Summary
Macrophages, which mean “big eaters” in Greek, are immune cells present in almost all tissues of the body with distinct tissue-specific phenotypes and functions. Macrophages can remove apoptotic cells by efferocytosis, a specialized form of phagocytosis, to prevent the induction of inflammation by the apoptotic cells [3] In addition to their role as guardians, macrophages play an essential role in organizing inflammatory reactions by producing pro- and anti-inflammatory mediators and effector molecules such as chemokines, cytokines, and growth factors [2]. Consistent with such a broad array of functions, macrophages are involved in various inflammatory disorders and pathological conditions, such as atherosclerosis, osteoporosis, neurodegenerative disorders, and autoimmune diseases [4]. We outline the existing data on expression and regulation of TGs in macrophages and elaborate on the distinct functions of TGs in monocytes and tissue-specific macrophages to improve our understanding of their contributions to various diseases
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
