* Lipopolysaccharide-Activated Canine Platelets Upregulate High Mobility Group Box-1 via Toll-Like Receptor 4.
- High mobility group box-1 (HMGB1) and the toll-like receptor 4 (TLR4) axis is a key mediator of inflammation. Platelet-derived high mobility group box-1 (HMGB1) may also play a critical role in sepsis-mediated thrombosis resulting in complications like disseminated intravascular coagulation and multiple organ failure. While elevated levels of HMGB1 have been documented in humans and dogs with systemic inflammatory response syndrome and sepsis, a better understanding of how platelet agonists and lipopolysaccharide (LPS) mediate platelet HMGB1 expression would open doors to novel therapies for sepsis-mediated thrombosis. Herein, we sought to determine if canine platelets express HMGB1 in the presence or absence of LPS and agonists (ADP or thrombin) and if surface expression of HMGB1 is dependent on platelet TLR4. Canine platelets were unstimulated (resting) or activated with thrombin or adenosine diphosphate (ADP) in the presence or absence of Escherichia coli LPS prior to flow cytometric and western blot analyses for HMGB1 expression. We also treated canine platelets with or without TLR4 function blocking antibody or its isotype control. We discovered that while thrombin upregulated both surface and cellular HMGB1 expression, LPS-mediated activation in the presence of ADP priming led to upregulation of surface HMGB1 expression. This expression was found to be most prominent in platelets that had undergone alpha-granule secretion. Inhibition of TLR4 attenuated LPS-induced HMGB1 expression indicating that exteriorization of HMGB1 may be dependent on the non-genomic pathway of platelet TLR4. Our findings indicate that upregulation of platelet-derived HMGB1 occurs as a result of thrombin or TLR4-mediated activation in dogs. Future studies should explore the translational implication of platelet-derived HMGB1 as novel therapeutic targets in humans and dogs with sepsis.
=>1.機能, 関数, 役割, 働き, 2.機能する, 作用する, 働く, 役目を果たす, 3.社交的会合, パーティー, 儀式
Overview of noun function
The noun function has 7 senses (first 3 from tagged texts)
1. (43) function, mathematical function, single-valued function, map, mapping -- ((mathematics) a
mathematical relation such that each element of a given set (the domain of the function) is
associated with an element of another set (the range of the function))
2. (24) function, purpose, role, use -- (what something is used for; "the function of an auger is to
bore holes"; "ballet is beautiful but what use is it?")
3. (7) function, office, part, role -- (the actions and activities assigned to or required or
expected of a person or group; "the function of a teacher"; "the government must do its part"; "play
its role")
4. function -- (a relation such that one thing is dependent on another; "height is a function of
age"; "price is a function of supply and demand")
5. function -- (a formal or official social gathering or ceremony; "it was a black-tie function")
6. affair, occasion, social occasion, function, social function -- (a vaguely specified social
event; "the party was quite an affair"; "an occasion arranged to honor the president"; "a seemingly
endless round of social functions")
7. routine, subroutine, subprogram, procedure, function -- (a set sequence of steps, part of larger
computer program)
Overview of verb function
The verb function has 3 senses (first 3 from tagged texts)
1. (9) function, work, operate, go, run -- (perform as expected when applied; "The washing machine
won't go unless it's plugged in"; "Does this old car still run well?"; "This old radio doesn't work
anymore")
2. (3) serve, function -- (serve a purpose, role, or function; "The tree stump serves as a table";
"The female students served as a control group"; "This table would serve very well"; "His freedom
served him well"; "The table functions as a desk")
3. (1) officiate, function -- (perform duties attached to a particular office or place or function;
"His wife officiated as his private secretary")
--- WordNet end ---