Microglia cells protect neurons by direct engulfment of invading neutrophil granulocytes-a new mechanism of CNS immune privilege

• Autorzy: Reymann K.G.
• Języki publikacji: EN

Abstrakty

EN

The central nervous system is an immune-privileged site, where immune responses are suppressed. Mechanisms described so far include the blood-brain barrier as well as, absence of co-stimulatory molecules and the expression of ligands inducing immune cell apoptosis in CNS tissue. On the other site, during ischemic tissue-damage such as stroke peripheral immune cells acutely infi ltrate the brain and may exacerbate neurodegeneration. In this study we investigate the impact of polymorphonuclear neutrophil granulocytes (PMN) on the viability of neurons in a situation of ischemic stress, where the blood-brain barrier loses its integrity. In this situation the major early cellular infi ltrate of ischemic lesions are PMNs. Here we demonstrate, that PMN as such are not toxic for neurons. However, under conditions of transient ischemia they potently enhance neuronal death. This, however, is effi ciently counteracted against by microglia, the resident phagocytic immune cells of the brain. By time-lapse imaging we demonstrate that this protection is mediated by direct phagocytosis of PMNs by microglia cells. Phagocytosis is not limited to apoptotic or dead PMNs but equally frequent and effi cient with fully viable and highly motile PMNs. In order to obtain phagocytosis microglial cells express highly motile cellular protrusions and even chasing behaviour, both, in intact hippocampal slices as well as in disseminated cell cultures. This phagocytosis is mediated by lektin- and integrinbased interaction. Importantly, specifi cally interfering with this function of microglia totally inhibits their neuroprotective function. While phagocytosis of apoptotic cells by macrophage-like cells is a common process, to the best of our knowledge the phagocytosis of live pro-infl ammatory immune cells by other immune cells of the body has never been observed before. Our demonstration that this can mediate a strong neuroprotective function suggests that this represents a previously not recognized pathway of the CNS immune privilege.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 1
• Opis fizyczny: p.92-93

Twórcy

autor

Reymann K.G.

• Leibniz Institute for Neurobiology, Magdeburg, Germany