Abstract
First discovered on macrophages by Goldstein and Brown in 1979, Scavenger Receptors have since been shown to participate in a diverse number of cell functions; equally diverse are their structures and the ligands they bind. Macrophage activation is crucial in the outcome of an immune response. SR-A1 is highly abundant on macrophages and recognizes both host- and microorganism-derived molecules that impact processes that are initiated, perpetuated, or modified. This review summarizes the involvement of SR-A1 in both inflammatory and anti-inflammatory responses, the multiple-ligand internalization mechanisms and the diversity of signaling pathways that impact macrophage function and activation. Engagement of SR-A1 results in the stimulation of differential signaling pathways and patterns of cytokine expression, kinetics, magnitude of response and activation status. SR-A1 plays essential roles in phagocytosis and efferocytosis, interacting with other receptors and promoting tolerance in response to apoptotic cell uptake. In cell adhesion, tissue remodeling, and cell migration, SR-A1 signals through different pathways engaging different cytoplasmic motifs. We describe the role of SR-A1 during innate and adaptive immune responses, such as participation in macrophage polarization and interaction with other innate receptors, as well as in antigen uptake, processing, and presentation, regulating T and B cell activation. The dichotomous contribution of SR-A1 on macrophage functions is discussed. A better understanding of the role SR-A1 plays through molecular mechanisms and crosstalk with other receptors may provide insights into developing novel therapeutic strategies to modulate immune responses and immunopathologies.
