When macrophages settle in tissues, they become tissue-resident macrophages in response to tissue-specific cues. As a result, each tissue has its own unique macrophage population, which has often distinctive traits and functions (Graphic Abstract 2). This chapter and those following review the functions governed by M2 macrophages in the major organ systems of the human body. We overview the tissue niches occupied by macrophages, the microenvironment in which they reside (e.g., cytokine milieu, exposure to signals of the surrounding cells), and the mutual interactions between macrophages and other elements of the tissues, such as cells and extracellular matrix components. The integument is the primary barrier of the body wherein M2 macrophages are associated with the skin and are called dermal macrophages. The dermal macrophages are members of immune-privileged compartments around the hair follicles and the nails, and interact with melanocytes of the epidermis. The musculoskeletal system or locomotor apparatus constructed of the integration of bones, joints, skeletal muscles, tendons, ligaments, and motor and sensory components of the nervous system. The musculoskeletal system allows voluntary body movement, although it also serves specific human traits such as manipulative tasks with extraordinary accuracy, gestural communication, and speech. The muscles also integrate intermediary metabolism; the bones maintain mineral homeostasis and host the hematopoietic compartment. M2 macrophages are mainly involved in the growth and repair processes of the skeletal elements, muscles, and tendons.
CPA was well tolerated at all dose levels (10-150 mg) following single oral dose administration to healthy male volunteers. There was no relationship between the intensity, duration and number of adverse events reported and the dose of CPA. There was a dose-related increase in exposure as measured by AUC0-infinity and Cmax. Administration of 10 mg CPA following food resulted in a delayed tmax, and a significant decrease in Cmax but not AUC0-infinity.
