Table.

What is known about the topic ?

Del-1 is an endogenous inhibitor of β2-integrin–dependent leukocyte infiltration. Previous studies suggested that exogenously administered Del-1 (administration of the recombinant protein or transient plasmid-driven overexpression) might promote angiogenesis. However, the role of endogenous Del-1 in angiogenesis was not studied so far.

What does this paper add ?

Intriguingly, our experiments revealed that endogenous Del-1 has a context-specific role in angiogenesis: While Del-1-deficiency is not affecting physiologic vascularization of the retina, endogenous Del-1 acts as an inhibitor of ischemia-induced angiogenesis, which is largely associated with inflammation. Mechanistically, the prevailing function of endogenous Del-1 is to limit ischemia-driven angiogenesis by inhibition of the LFA-1-integrin-dependent homing of hematopoietic cells and immune cells to ischemic tissues. Consistently, lack of hematopoietic LFA-1 reversed the enhanced ischemia-driven angiogenesis due to Del-1-deficiency. Our present findings reveal a new unrecognized function of endogenous Del-1 as a local inhibitor of ischemia-induced angiogenesis by restraining LFA-1–dependent homing of pro-angiogenic hematopoietic and immune cells to ischemic tissues. Furthermore, our present findings extend and improve the current models for understanding inflammation-related angiogenesis by shedding light on the role of endogenous inflammation inhibitors such as Del-1.