We investigate how leukocytes are rapidly targeted to sites of “danger” in intact tissues, i.e. how they detect wounds or sites of infection. Misregulation of this process may lead to hyper-inflammatory disease. Chronic inflammatory states, in turn, promote cancer. Although the complex cytokine networks that govern amplification and resolution of inflammatory responses have been intensely studied, the initial mechanisms that regulate leukocyte targeting in tissues remain very little understood.