British Heart Foundation (PG/12/68/29779 and
PG/14/48/30916) and the Wellcome Trust (101604/Z/13/Z to SN and TW, and
098291/Z/12/Z to S.N)

Abbott

Altieri

Alugupalli

Armstrong

Cattaneo

Chan

Clark

di Minno

D’Souza

Freyer

Harrison

Hirsh

Iyú

Kevil

Kirkby

Konstantopoulos

Languino

Lordkipanidzé

McCaffery

Melissa V. Chan

Michaela Finsterbusch

Michelson

Nakamura

Nancy Hogg

Nicholas S. Kirkby

Patrono

Paul

Paul C. J Armstrong

Projahn

Rand

Shankar

Sussan Nourshargh

Threadgill

Timothy D. Warner

Turner

von Brühl

Warner

Woulfe

Blood

PubMed

Key PointsLow-volume, high-throughput whole blood aggregometry will facilitate future mouse platelet function research. Application of this approach identifies ICAM-1 as a novel mediator of platelet-monocyte interaction through fibrinogen binding.</jats:p

Crossref

Novel whole blood assay for phenotyping platelet reactivity in mice identifies ICAM-1 as a mediator of platelet-monocyte interaction

Testing of platelet function is central to the cardiovascular phenotyping of genetically modified mice. Traditional platelet function tests have been developed primarily for testing human samples and the volumes required make them highly unsuitable for the testing of mouse platelets. This limits research in this area. To address this problem, we have developed a miniaturized whole blood aggregometry assay, based on a readily accessible 96-well plate format coupled with quantification of single platelet depletion by flow cytometric analysis. Using this approach, we observed a concentration-dependent loss of single platelets in blood exposed to arachidonic acid, collagen, U46619 or protease activated receptor 4 activating peptide. This loss was sensitive to well-established antiplatelet agents and genetic manipulation of platelet activation pathways. Observations were more deeply analyzed by flow cytometric imaging, confocal imaging, and measurement of platelet releasates. Phenotypic analysis of the reactivity of platelets taken from mice lacking intercellular adhesion molecule (ICAM)-1 identified a marked decrease in fibrinogen-dependent platelet-monocyte interactions, especially under inflammatory conditions. Such findings exemplify the value of screening platelet phenotypes of genetically modified mice and shed further light upon the roles and interactions of platelets in inflammation

Armstrong, PCJ

Kirkby, NS

Chan, MV

Finsterbusch, M

Hogg, N

Nourshargh, S

Warner, TD

Spiral - Imperial College Digital Repository

Queen Mary Research Online

https://qmro.qmul.ac.uk/xmlui/bitstream/handle/123456789/15669/Armstrong%20Novel%20whole%20blood%20assay%20accepted%202015.pdf?sequence=3

Novel whole blood assay for phenotyping platelet reactivity in mice identifies ICAM-1 as a mediator of platelet-monocyte interaction

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Crossref

Spiral - Imperial College Digital Repository

Queen Mary Research Online