Document Detail

Human eosinophil chemotaxis and selective in vivo recruitment by sphingosine 1-phosphate.
MedLine Citation:
PMID:  15254297     Owner:  NLM     Status:  MEDLINE    
Sphingosine 1-phosphate (S1P) is a sphingolipid mediator that is involved in diverse biological functions. Local administration of S1P causes inflammation coupled to a large eosinophil (EO) recruitment in the rat-paw tissue. The inflammatory response is accompanied by an increase in S1P receptors, namely S1P(1), S1P(2), S1P(3), and by an enhanced expression of CCR3, which is the main chemokine receptor known to be involved in EO function. Human EOs constitutively express S1P(1) and, at a lower extent, S1P(2), S1P(3) receptors. S1P in vitro causes cultured human EO migration and an increase in S1P receptor mRNA copies and strongly up-regulates CCR3 and RANTES (regulated on activation, normal T cell-expressed and secreted) message levels; in particular CCR3 is up-regulated 18,000-fold by S1P. A blocking anti-CCR3 Ab inhibits S1P-induced chemotaxis, implying that S1P acts as specific recruiting signal for EOs not only through its own receptors but also through CCR3. These results show that S1P is involved in EO chemotaxis and contribute to shed light on the complex mechanisms underlying EO recruitment in several diseases such as asthma and some malignancies.
Fiorentina Roviezzo; Francesco Del Galdo; Gianfranco Abbate; Mariarosaria Bucci; Bruno D'Agostino; Edson Antunes; Gianfranco De Dominicis; Luca Parente; Francesco Rossi; Giuseppe Cirino; Raffaele De Palma
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-07-14
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  101     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-07-28     Completed Date:  2004-08-25     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11170-5     Citation Subset:  IM    
Dipartimento di Scienze Farmaceutiche, Università di Salerno, 84084 Salerno, Italy.
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MeSH Terms
Chemokine CCL5 / genetics
Chemotaxis, Leukocyte / drug effects,  physiology*
Edema / chemically induced,  pathology
Eosinophils / drug effects,  physiology*
Flow Cytometry
Gene Expression Regulation / drug effects
Lysophospholipids / pharmacology*
Receptors, CCR3
Receptors, Chemokine / drug effects,  genetics
Sphingosine / analogs & derivatives,  pharmacology*
Reg. No./Substance:
0/CCR3 protein, human; 0/Ccr3 protein, rat; 0/Chemokine CCL5; 0/Lysophospholipids; 0/Receptors, CCR3; 0/Receptors, Chemokine; 123-78-4/Sphingosine; 26993-30-6/sphingosine 1-phosphate

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