LRG1 destabilizes tumor vessels and restricts immunotherapeutic potency.

Background: A poorly functioning tumor vasculature is pro-oncogenic and may impede the delivery of therapeutics. Normalizing the vasculature, therefore, may be beneficial. We previously reported that the secreted glycoprotein leucine-rich α-2-glycoprotein 1 (LRG1) contributes to pathogenic neovascularization.

Soluble CD93 is an apoptotic cell opsonin recognized by α β.

Efferocytosis is essential for homeostasis and prevention of the inflammatory and autoimmune diseases resulting from apoptotic cell lysis. CD93 is a transmembrane glycoprotein previously implicated in efferocytosis, with mutations in CD93 predisposing patients to efferocytosis-associated diseases. CD93 is a cell surface protein, which is proteolytically shed under inflammatory conditions, but it is unknown how CD93 mediates efferocytosis or whether its efferocytic activity is mediated by the soluble or membrane-bound form.

Antagonistic Coevolution of MER Tyrosine Kinase Expression and Function.

TYRO3, AXL, and MERTK (TAM) receptors are a family of receptor tyrosine kinases that maintain homeostasis through the clearance of apoptotic cells, and when defective, contribute to chronic inflammatory and autoimmune diseases such as atherosclerosis, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and Crohn's disease. In addition, certain enveloped viruses utilize TAM receptors for immune evasion and entry into host cells, with several viruses preferentially hijacking MERTK for these purposes. Despite the biological importance of TAM receptors, little is understood of their recent evolution and its impact on their function.

Quantitative Efferocytosis Assays.

Efferocytosis, the phagocytic removal of apoptotic cells, is a dynamic process requiring recruitment of numerous regulatory proteins to forming efferosomes in a tightly regulated manner. Herein we describe microscopy-based methods for the enumeration of efferocytic events and characterization of the spatiotemporal dynamics of signaling molecule recruitment to efferosomes, using genetically encoded probes and immunofluorescent labeling. While these methods are illustrated using macrophages, they are applicable to any efferocytic cell type.