Macrophages and the maintenance of homeostasis

Abstract

There have been many chapters written about macrophage polarization. These chapters generally focus on the role of macrophages in orchestrating immune responses by highlighting the T-cell-derived cytokines that shape these polarizing responses. This bias toward immunity is understandable, given the importance of macrophages to host defense. However, macrophages are ubiquitous and are involved in many different cellular processes, and describing them as immune cells is undoubtedly an oversimplification. It disregards their important roles in development, tissue remodeling, wound healing, angiogenesis, and metabolism, to name just a few processes. In this chapter, we propose that macrophages function as transducers in the body. According to Wikipedia, "A transducer is a device that converts energy from one form to another." The word transducer is a term used to describe both the "sensor," which can interpret a wide range of energy forms, and the "actuator," which can switch voltages or currents to affect the environment. Macrophages are able to sense a seemingly endless variety of inputs from their environment and transduce these inputs into a variety of different response outcomes. Thus, rather than functioning as immune cells, they should be considered more broadly as cellular transducers that interpret microenvironmental changes and actuate vital tissue responses. In this chapter, we will describe some of the sensory stimuli that macrophages perceive and the responses they make to these stimuli to achieve their prime directive, which is the maintenance of homeostasis.

Keywords: Macrophages; cytokines; development; inflammation; polarization.

Fig. 1

Macrophages as transducers. An analogy was made regarding macrophages functioning as a transducer of information to generate a model. a Macrophages from different tissues function by collecting information from the microenvironment, processing this information, and transducing it to generate important chemical responses for the specific functioning of an individual organ. b Different stimuli or combinations of stimuli, which are depicted as different forms of energy, are received by macrophages and transduced into different outputs. This image was prepared using Medical ART (https://smart.servier.com/)

Fig. 2

Macrophage responses to endogenous and exogenous regulators. Left: stimulated macrophages produce and release ATP. The macrophage ectoenzymes CD39 and CD73 rapidly convert ATP to adenosine, which signals through high-affinity receptors for adenosine to switch off the production of inflammatory mediators and to induce the production of growth-associated and angiogenic factors. Stimulated human macrophages also upregulate the synthesis of PGE₂ and the receptors for PGE₂, causing them to become exquisitely sensitive to the regulatory effects of PGE₂. Macrophages also catabolize lipids into lipoxins and resolvins to dampen inflammatory responses. Right: neighboring cells, including fibroblasts, endothelial cells, neutrophils, and platelets, can also be a source of these regulatory molecules. These neighboring cells can also be stimulated to produce “enhancer” molecules that amplify the initial activation response. This image was prepared using Medical ART (https://smart.servier.com/)