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Severe meningococcal disease is characterized by early neutrophil but not platelet activation and increased formation and consumption of platelet-neutrophil complexes

Peters, M.J., Heyderman, R.S., Faust, S., Dixon, G.L., Inwald, D.P. and Klein, N.J. (2003) Severe meningococcal disease is characterized by early neutrophil but not platelet activation and increased formation and consumption of platelet-neutrophil complexes Journal of Leukocyte Biology, 73, (6), pp. 722-730. (doi:10.1189/jlb.1002509).

Record type: Article

Abstract

Approximately 25% of polymorphonuclear leukocytes (PMNL) circulate in heterotypic complexes with one or more activated platelets. These platelet–neutrophil complexes (PNC) require platelet CD62P expression for their formation and represent activated subpopulations of both cell types. In this study, we have investigated the presence, time course, and mechanisms of PNC formation in 32 cases of severe pediatric meningococcal disease (MD) requiring intensive care.
There were marked early increases in PMNL CD11b/CD18 expression and activation, and reduced CD62L expression compared with intensive care unit control cases. Minimal platelet expression of the active form of IIbß3 (GpIIb/IIIa) was seen. PNC were reduced on presentation and fell to very low levels after 24 h. Immunostaining of skin biopsies demonstrated that PNC appear outside the circulation in MD.
In vitro studies of anticoagulated whole blood inoculated with Neisseria meningitidis supported these clinical findings with marked increases in PMNL CD11b/CD18 expression and activation but no detectable changes in platelet-activated IIbß3 or CD62P expression. In vitro PMNL activation with N. meningitidis (or other agonists) potentiated the formation of PNC in response to platelet activation with adenine diphosphate. Therefore, in severe MD, PMNL activation is likely to promote PNC formation, and we suggest that the reduced levels of PNC seen in established MD reflect rapid loss of PNC from the circulation rather than reduced formation.

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More information

Published date: 2003
Keywords: sepsis, adhesion, meningococcus, inflammation

Identifiers

Local EPrints ID: 40618
URI: http://eprints.soton.ac.uk/id/eprint/40618
ISSN: 0741-5400
PURE UUID: 9da9b443-5d6d-48ae-910d-911515f894ef
ORCID for S. Faust: ORCID iD orcid.org/0000-0003-3410-7642

Catalogue record

Date deposited: 07 Jul 2006
Last modified: 16 Apr 2017 21:51

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Contributors

Author: M.J. Peters
Author: R.S. Heyderman
Author: S. Faust ORCID iD
Author: G.L. Dixon
Author: D.P. Inwald
Author: N.J. Klein

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