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Human platelets exhibit chemotaxis using functional N-formyl peptide receptors.

Abstract：

OBJECTIVE:Activated platelets participate in inflammatory and microbicidal processes by upregulation of surface selectins, shedding of CD40 ligand, and release of platelet microbicidal proteins and microparticles. Given their myeloid lineage, we hypothesized that platelets express functional N-formyl peptide receptors and respond to the bacterially derived chemotactic peptide N-formyl peptide with gradient-driven chemotaxis. METHODS AND RESULTS:Here we show specific binding of N-formyl peptides to the surface of activated platelets. Platelet expression and function of the formyl peptide receptor, FPR, was verified by RT-PCR of the differentiated megakaryocyte MEG-01 cell line, immunoblotting of platelet proteins, and calcium mobilization in platelets with formyl peptide binding. Furthermore, we demonstrate gradient-driven chemotaxis of platelets by video microscopy and transwell migration toward formyl peptides. We also show that endogenous formyl peptides, released by eukaryotic mitochondria from necrotic cells, induce chemotaxis using formyl peptide receptors expressed by thrombin-activated platelets. Conversely, supernatants from cells undergoing apoptotic cell death do not induce platelet chemotaxis. Platelet chemotaxis to formyl peptides was blocked with FPR-specific antibody as well as by pertussis toxin inhibition of the formyl peptide G-coupled receptor. CONCLUSION:These data establish a new role for platelets in host defense and suggest reexamination of their active function in microbicidal and other host defense activities.

journal_name

Exp Hematol

journal_title

Experimental hematology

authors

Czapiga M,Gao JL,Kirk A,Lekstrom-Himes J

doi

10.1016/j.exphem.2004.09.010

keywords:

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

73-84

issue

1

eissn

0301-472X

issn

1873-2399

pii

S0301-472X(04)00351-0

journal_volume

33

pub_type

杂志文章

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