Blood flow patterns spatially associated with platelet aggregates in murine colitis.
In the normal murine mucosal plexus, blood flow is generally smooth and continuous. In inflammatory conditions, such as chemically-induced murine colitis, the mucosal plexus demonstrates markedly abnormal flow patterns. The inflamed mucosal plexus is associated with widely variable blood flow velocity as well as discontinuous and even bidirectional flow. To investigate the mechanisms responsible for these blood flow patterns, we used intravital microscopic examination of blood flow within the murine mucosal plexus during dextran sodium sulphate-and trinitrobenzenesulfonic acid-induced colitis. The blood flow patterns within the mucosal plexus demonstrated flow exclusion in 18% of the vessel segments (P < 0.01). Associated with these segmental exclusions was significant variation in neighboring flow velocities. Intravascular injection of fluorescent platelets demonstrated platelet incorporation into both fixed and rolling platelet aggregates. Rolling platelet aggregates (mean velocity 113 microm/sec; range, 14-186 microm/sec) were associated with reversible occlusions and flow variations within the mucosal plexus. Gene expression profiles of microdissected mucosal plexus demonstrated enhanced expression of genes for CCL3, CXCL1, CCL2, CXCL5, CCL7, CCL8, and Il-1b (P < 0.01), and decreased expression of CCL6 (P < 0.01). These results suggest that platelet aggregation, activated by the inflammatory mileau, contributes to the complex flow dynamics observed in acute murine colitis.
Miele
Lino F
LF
Laboratory of Adaptive and Regenerative Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Turhan
Aslihan
A
Lee
Grace S
GS
Lin
Miao
M
Ravnic
Dino
D
Tsuda
Akira
A
Konerding
Moritz A
MA
Mentzer
Steven J
SJ
D000208:Acute Disease; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000503:physiopathology*; D016264:Dextran Sulfate / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000503:physiopathology; D020869:Gene Expression Profiling; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000098:blood supply*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D010974:Platelet Aggregation; D012039:Regional Blood Flow; D014302:Trinitrobenzenesulfonic Acid / Q000009:adverse effects
D018925:Chemokines; D053583:Interleukin-1beta; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate