Document Detail


Painful stimulation suppresses joint inflammation by inducing shedding of L-selectin from neutrophils.
MedLine Citation:
PMID:  10470085     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although the inflammatory response is essential for protecting tissues from injury and infection, unrestrained inflammation can cause chronic inflammatory diseases such as arthritis, colitis and asthma. Physiological mechanisms that downregulate inflammation are poorly understood. Potent control might be achieved by regulating early stages in the inflammatory response, such as accumulation of neutrophils at the site of injury, where these cells release chemical mediators that promote inflammatory processes including plasma extravasation, bacteriocide and proteolysis. To access an inflammatory site, neutrophils must first adhere to the vascular endothelium in a process mediated in part by the leukocyte adhesion molecule L-selectin. This adhesion is prevented when L-selectin is shed from the neutrophil membrane. Although shedding of L-selectin is recognized as a potentially important mechanism for regulating neutrophils, its physiological function has not been demonstrated. Shedding of L-selectin may mediate endogenous downregulation of inflammation by limiting neutrophil accumulation at inflammatory sites. Here we show that activation of nociceptive neurons induces shedding of L-selectin from circulating neutrophils in vivo and that this shedding suppresses an ongoing inflammatory response by inhibiting neutrophil accumulation. These findings indicate a previously unknown mechanism for endogenous feedback control of inflammation. Failure of this mechanism could contribute to the etiology of chronic inflammatory disease.
Authors:
H J Strausbaugh; P G Green; E Lo; K Tangemann; D B Reichling; S D Rosen; J D Levine
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Nature medicine     Volume:  5     ISSN:  1078-8956     ISO Abbreviation:  Nat. Med.     Publication Date:  1999 Sep 
Date Detail:
Created Date:  1999-09-24     Completed Date:  1999-09-24     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9502015     Medline TA:  Nat Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1057-61     Citation Subset:  IM    
Affiliation:
NIH Pain Center, UCSF, 521 Parnassus Avenue, San Francisco, California 94143-0440, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arthritis / blood,  pathology,  physiopathology*
Bradykinin / antagonists & inhibitors,  pharmacology
Cells, Cultured
Down-Regulation
Electric Stimulation
Feedback
Flow Cytometry
Hindlimb
Hydroxamic Acids*
L-Selectin / metabolism*
Male
Neurons, Afferent / physiology
Neutrophils / metabolism*,  physiology
Nociceptors / physiology
Pain / blood,  physiopathology*
Protease Inhibitors / pharmacology
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
AM32624/AM/NIADDK NIH HHS
Chemical
Reg. No./Substance:
0/Hydroxamic Acids; 0/Protease Inhibitors; 0/Ro 31-9790; 126880-86-2/L-Selectin; 58-82-2/Bradykinin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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