The chemokine system -- a major regulator of angiogenesis in health and disease

Abstract

The chemokine system controls leukocyte trafficking during homeostasis as well as during inflammation and is necessary for the linkage between innate and adaptive immunity. Tissue regulation outside the hematopoietic compartment, for instance, angiogenesis, organogenesis and tumor development, growth and metastasis, is another important function of the chemokine system. The chemokine-mediated regulation of angiogenesis is highly sophisticated and fine tuned, and involves pro-angiogenic chemokines, for instance, CXCL8/IL8 interacting with the CXCR2 receptor, and anti-angiogenic (i.e. angiostatic) chemokines, for instance, CXCL10/IP10 interacting with the CXCR3 receptor. Chemokines also regulate angiogenesis in a receptor-independent manner by means of a perturbation of bFGF and VEGF function. The current review focuses on the influence of the chemokine system in angiogenesis. Examples of the delicate angiogenesis regulation by the chemokine system in, for instance, wound healing and of the dysregulation in, for instance, tumor development are provided along with the interesting phenomenon of molecular piracy of host-encoded genes within the chemokine system. This phenomenon is a general strategy to circumvent and exploit the immune system -- and thereby improve survival -- for many viruses. Yet, a certain group of herpesviruses -- the gamma2-herpesviruses -- encode a functional CXCR2 receptor homolog that is activated by angiogenic chemokines and antagonized by angiostatic chemokines, and this particular gene seems to cause the development of a vascular tumor -- Kaposi's sarcoma -- in the host.