Abstract：
:Alarmins are preformed, endogenous molecules that can be promptly released to signal cell or tissue stress or damage. The ubiquitous nuclear molecule high-mobility group box 1 protein (HMGB1) is a prototypical alarmin activating innate immunity. HMGB1 serves a dual alarmin function. The protein can be emitted to alert adjacent cells about endangered homeostasis of the HMGB1-releasing cell. In addition to this expected path of an alarmin, extracellular HMGB1 can be internalized via RAGE-receptor mediated endocytosis to the endolysosomal compartment while attached to other extracellular proinflammatory molecules. The endocytosed HMGB1 may subsequently destabilize lysosomal membranes. The HMGB1-bound partner molecules depend on the HMGB1-mediated transport and the induced lysosomal leakage to obtain access to endosomal and cytosolic reciprocal sensors to communicate extracellular threat and to initiate the proper activation pathways.
journal_name
Semin Immunoljournal_title
Seminars in immunologyauthors
Andersson U,Yang H,Harris Hdoi
10.1016/j.smim.2018.02.011subject
Has Abstractpub_date
2018-08-01 00:00:00pages
40-48eissn
1044-5323issn
1096-3618pii
S1044-5323(17)30076-3journal_volume
38pub_type
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