Journal
JOURNAL OF IMMUNOLOGY
Volume 182, Issue 1, Pages 572-580Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.182.1.572
Keywords
-
Categories
Funding
- National Institutes of Health [R01-HL-079669, P50-GM-53799]
- Veterans Affairs Merit Award
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL079669] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR059647] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK072230] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P50GM053789] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Polymorphonuclear neutrophils (PMN) are critical innate immune effector cells that either protect the host or exacerbate organ dysfunction by migrating to injured or inflamed tissues. Resuscitated hemorrhagic shock following major trauma promotes the development of organ inflammation by priming PMN migration and activation in response to a second, often trivial, stimulus (a so-called two hit phenomenon). PMN mobilization from bone marrow supports a sustained, hemorrhagic shock/resuscitation (HS/R)-primed migration of PMN. We addressed the role and mechanism of HS/R in regulating PMN egress from bone marrow. We demonstrate that HS/R through the alarmin HMGB1 induces IL-23 secretion from macrophages in an autocrine and TLR4 signaling-dependent manner. In turn IL-23, through an IL-17 G-CSF-mediated mechanism, induces PMN egress from bone marrow. We also show that beta-adrenergic receptor activation by catecholamine of macrophages mediates the HS/R-induced release of HMGB1. These data indicate that HS/R, a global ischemia/reperfusion stimulus, regulates PMN mobilization through a series of interacting pathways that include neuroendocrine and innate and acquired immune systems. Blocking this novel signaling axis may present a novel therapeutic target for posttrauma inflammation. The Journal of Immunology, 2009, 182: 572-580.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available