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PMID: 9329974 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Neutrophil accumulation on activated, surface-adherent platelets in flow is mediated by interaction of Mac-1 with fibrinogen bound to alphaIIbbeta3 and stimulated by platelet-activating factor.

The Journal of clinical investigation ·Vol. 100 ·No. 8 ·1997-10-15 ·Pages 2085-93

Weber C, Springer TA

Abstract

We have studied the pathways that lead to arrest and firm adhesion of rolling PMN on activated, surface-adherent platelets. Stable arrest and adhesion strengthening of PMN on thrombin-stimulated, surface-adherent platelets in flow required distinct Ca2+- and Mg2+-dependent regions of Mac-1 (alphaMbeta2), and involved interactions of Mac-1 with fibrinogen, which was bound to platelets via alphaIIbbeta3. Mac-1 also bound to other unidentified ligands on platelets, which were not intracellular adhesion molecule-2 (ICAM-2), heparin, or heparan-sulfate proteoglycans. This was shown by inhibition with mAbs or peptides, by treatment of platelets with heparitinase, and by using platelets with defective alphaIIbbeta3 from a patient with Glanzmann thrombasthenia. Tethering of PMN on platelet ICAM-2 via LFA-1 (alphaLbeta2) was observed, which may facilitate the transition between rolling on selectins and Mac-1-dependent arrest. Arrest and adhesion strengthening was pertussis toxin sensitive and in flow was mainly induced by platelet-activating factor but not through activation of the chemokine receptor CXCR2. In stasis, spreading occurred and the CXCR2 contributed to firm adhesion.

MeSH Terms
Antigens, CD/metabolism Blood Platelets/physiology Calcium/pharmacology Cell Adhesion/drug effects Cell Adhesion Molecules/metabolism Fibrinogen/metabolism Humans Integrins/metabolism Lymphocyte Function-Associated Antigen-1/metabolism Macrophage-1 Antigen/metabolism Magnesium/pharmacology Movement Neutrophils/physiology Platelet Activating Factor/metabolism Platelet Activation Platelet Glycoprotein GPIIb-IIIa Complex/genetics,metabolism Thrombasthenia/metabolism
Chemicals
Antigens, CD Cell Adhesion Molecules ICAM2 protein, human Integrins Lymphocyte Function-Associated Antigen-1 Macrophage-1 Antigen Platelet Activating Factor Platelet Glycoprotein GPIIb-IIIa Complex Fibrinogen Magnesium Calcium
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Weber C
The Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Springer T A
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI119742
Published
1997-10-15
Pages
2085-93
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC508400
Subset
IM
Grants
NHLBI NIH HHS · HL-48675 · United States
External Links
PubMed source DOI: 10.1172/JCI119742 PMC Full Text View journal details
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