Abstract
Immune cell recruitment and migration is central to the normal functioning of the immune system in health and disease. Numerous adhesion molecules on immune cells and the parenchymal cells they interact with are well recognized for their roles in facilitating the movements of immune cells throughout the body. A growing body of evidence now indicates that tetraspanins, proteins known for their capacity to organize partner molecules within the cell membrane, also have significant impacts on the ability of immune cells to migrate around the body. In this review, we examine the tetraspanins expressed by immune cells and endothelial cells that influence leukocyte recruitment and motility and describe their impacts on the function of adhesion molecules and other partner molecules that modulate the movements of leukocytes. In particular, we examine the functional roles of CD9, CD37, CD63, CD81, CD82, and CD151. This reveals the diversity of the functions of the tetraspanin family in this setting, both in the nature of adhesive and migratory interactions that they regulate, and the positive or inhibitory effects mediated by the individual tetraspanin proteins.
Highlights
The ability of leukocytes to migrate from the circulation to sites of inflammation is essential for effective host defense
The selectin family consists of three members; L-selectin, which is constitutively expressed on leukocytes [15], and E- and P-selectin, found on activated endothelial cells [16,17,18]
Recent super-resolution microscopy studies indicate a considerable heterogeneity among tetraspanin-enriched microdomains (TEMs), in that tetraspanins such as CD53 form nanoclusters in the plasma membrane, and are more likely to be directly associated with non-tetraspanin partners than with other tetraspanin family members [52]
Summary
The ability of leukocytes to migrate from the circulation to sites of inflammation is essential for effective host defense. To undertake this journey, leukocytes undergo a series of interactions in the bloodstream with endothelial cells lining the vasculature [1, 2]. In adaptive immunity, the recirculation and trafficking of B and T lymphocytes is crucial to ongoing surveillance against potential invading pathogens [2]. In both cases, leukocytes leave the bloodstream via a sequence of steps, collectively known as the leukocyte recruitment cascade
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