Thursday, February 28, 2013

Neutrophils Usher Monocytes Into Sites of Inflammation

Our researchers need to understand this if we truly want to prevent strokes and clean up after the damage.
http://circres.ahajournals.org/content/112/5/744.extract.html?etoc
One of the key processes of inflammation is the transmigration of circulating leukocytes across the endothelium. Among the leukocytes, neutrophils and monocytes are large phagocytes that can respond quickly to infection or injury. On sensing danger, neutrophils and monocytes adhere to the endothelium and transmigrate to the adjacent tissue via the coordinated activities of adhesion molecules, integrins, cytokines, and chemokines.1 Once they accumulate, these myeloid cells participate in a myriad of immune inflammatory activities. The importance of this event cannot be understated, especially because the accumulation of leukocytes in tissue is a double-edged sword. On the one hand, coordinated leukocyte accumulation in injured or infected sites is required for effective pathogen elimination and tissue healing. On the other hand, uncontrolled accumulation is a defining feature of chronic diseases, such as atherosclerosis.2 Understanding leukocyte migration is essential to understanding the immune system.
Article, see p 792
Neutrophils and monocytes do not accumulate all at once. In a typical acute inflammatory response, there is a well-defined sequence: neutrophils accumulate first; monocytes accumulate second. Among the monocytes, of which ≥2 subsets circulate in the mouse and human, there is yet another sequence: inflammatory murine Ly-6Chigh monocytes accumulate first and reparative Ly-6Clow monocytes accumulate second.3 This temporal (neutrophil ––> Ly-6Chigh monocyte ––> Ly-6Clow monocyte) hierarchy of accumulation is likely required for an effective innate response. The subsets, which have overlapping but also specialized functions, contribute sequentially to processes that involve pathogen elimination, efferocytosis, restoration of tissue integrity,
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