Perizyten als Leitstrukturen der interstitiellen Leukozytenmigration bei steriler Inflammation
This Thesis identifies NG2+pericytes as essential structures for interstitial leukocyte trafficking during sterile inflammation. It shows that the trafficking is orchestrated by more than just soluble chemokines. A mouse model was established to visualize via 2-Photon microscopy sterile inflammation and induce a focal sterile necrosis in the skin of the ear. The in vivo results show, that there are dynamic interactions between NG2+pericytes and myeloid leukocytes. Those interactions are
... actions are mediated by ICAM-1 which is expressed and upregulated by NG2+pericytes after sensing a sterile inflammation. A diffuse sterile inflammation induces myeloid leukocytes to accumulate along capillary NG2+pericytes and to interact with them. The analysis of the dynamic interactions between myeloid leukocytes and NG2+pericytes shows that the NG2+pericytes attract the myeloid leukocytes. In addition, there are chemotactic and haptotactic interactions between them. After inducing a focal sterile necrosis there are as well haptotactic and chemotactic interactions between NG2+pericytes and myeloid leukocytes. Though they are much shorter due to the fact that there is an additional local inflammatory stimulus. Furthermore, it showed that these interactions are beneficial for the myeloid leukocyte trafficking. The myeloid leukocytes are activated by the interaction, therefore migrate faster and in a more directional manner, consequently being much more effective. It became clear in vivo and in vitro that during sterile inflammation NG2+pericytes express and secrete MIF, a chemotactic molecule. MIF secreted by NG2+pericytes is required in vivo for the guidance and establishing migratory cues that provide myeloid leukocytes with the ability to effectively reach a focal sterile inflammation in the interstitial tissue. Hence NG2+pericytes are vital for the interstitial myeloide leukocyte trafficking during sterile inflammation.