The internalization and intracellular degradation of pathogens by macrophages is an essential part of the mammalian immune response. The intracellular transport of the phagosome from cell periphery to the perinuclear region subsequent to their internalization is crucial for the phagosomal maturation and digestion. This process shows high phagosome-to-phagosome variations that are not fully understood. To date mainly biochemical modulations are known to influence the fate of phagosomes. In the present work it could be shown that the phagosomal transport behaviour is also strongly influenced by simple physical properties of the phagosome: it’s size. It was shown that large phagosomes are transported persistently and with a high efficiency to the nucleus with almost no centrifugal motion, whereas small phagosomes show strong bidirectional transport, resulting in a reduced transport efficiency. Additionally small phagosomes show strong centrifugal transport compared to intermediate and large phagosomes, indicating a missing endpoint of phagosomal transport. By investigating the molecular basis of intracellular organelle transport it could be shown that dynein motors and the distribution of microtubules have a high impact on the persistent, centripetal transport of large phagosomes. Furthermore it was shown that actin filament associated motor activity and the distribution of actin filaments highly influence the bidirectional transport behaviour of small phagosomes as well as supporting the transport of all phagosomes. The demonstrated results suggest a simple size-dependent intracellular sorting mechanism that supports transport from cell periphery to the perinuclear region of large phagocytosed bacteria for facilitating their digestion and that simultaneously supports transport back to the cell periphery of small bacterial fragments for antigen presentation or disposal processes.
|School:||Universitaet Bayreuth (Germany)|
|Source:||DAI-C 81/2(E), Dissertation Abstracts International|
|Subjects:||Cellular biology, Immunology|
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