Platelet activation in cystic fibrosis

Brian P. O'Sullivan, Matthew D. Linden, Andrew L. Frelinger, Marc R. Barnard, Michele Spencer-Manzon, James E. Morris, Raneem O. Salem, Michael Laposata, Alan D. Michelson

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Cystic fibrosis (CF) is caused by a mutation of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). We examined platelet function in CF patients because lung inflammation is part of this disease and platelets contribute to inflammation. CF patients had increased circulating leukocyte-platelet aggregates and increased platelet responsiveness to agonists compared with healthy controls. CF plasma caused activation of normal and CF platelets; however, activation was greater in CF platelets. Furthermore, washed CF platelets also showed increased reactivity to agonists. CF platelet hyperreactivity was incompletely inhibited by prostaglandin E1 (PGE1). As demonstrated by Western blotting and reverse- transcriptase-polymerase chain reaction (RT-PCR), there was neither CFTR nor CFTR-specific mRNA in normal platelets. There were abnormalities in the fatty acid composition of membrane fractions of CF platelets. In summary, CF patients have an increase in circulating activated platelets and platelet reactivity, as determined by monocyte-platelet aggregation, neutrophil-platelet aggregation, and platelet surface P-selectin. This increased platelet activation in CF is the result of both a plasma factor(s) and an intrinsic platelet mechanism via cyclic adenosine monophosphate (cAMP)/adenylate cyclase, but not via platelet CFTR. Our findings may account, at least in part, for the beneficial effects of ibuprofen in CF.

Original languageEnglish (US)
Pages (from-to)4635-4641
Number of pages7
JournalBlood
Volume105
Issue number12
DOIs
StatePublished - Jun 15 2005
Externally publishedYes

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Platelet Activation
Platelets
Cystic Fibrosis
Blood Platelets
Chemical activation
Cystic Fibrosis Transmembrane Conductance Regulator
Platelet Aggregation
Agglomeration
Intrinsic Factor
P-Selectin
Alprostadil
Ibuprofen
Plasmas
Reverse Transcriptase Polymerase Chain Reaction
Gene encoding
Adenylyl Cyclases
Cyclic AMP
Polymerase chain reaction
RNA-Directed DNA Polymerase
Monocytes

ASJC Scopus subject areas

  • Hematology

Cite this

O'Sullivan, B. P., Linden, M. D., Frelinger, A. L., Barnard, M. R., Spencer-Manzon, M., Morris, J. E., ... Michelson, A. D. (2005). Platelet activation in cystic fibrosis. Blood, 105(12), 4635-4641. https://doi.org/10.1182/blood-2004-06-2098

Platelet activation in cystic fibrosis. / O'Sullivan, Brian P.; Linden, Matthew D.; Frelinger, Andrew L.; Barnard, Marc R.; Spencer-Manzon, Michele; Morris, James E.; Salem, Raneem O.; Laposata, Michael; Michelson, Alan D.

In: Blood, Vol. 105, No. 12, 15.06.2005, p. 4635-4641.

Research output: Contribution to journalArticle

O'Sullivan, BP, Linden, MD, Frelinger, AL, Barnard, MR, Spencer-Manzon, M, Morris, JE, Salem, RO, Laposata, M & Michelson, AD 2005, 'Platelet activation in cystic fibrosis', Blood, vol. 105, no. 12, pp. 4635-4641. https://doi.org/10.1182/blood-2004-06-2098
O'Sullivan BP, Linden MD, Frelinger AL, Barnard MR, Spencer-Manzon M, Morris JE et al. Platelet activation in cystic fibrosis. Blood. 2005 Jun 15;105(12):4635-4641. https://doi.org/10.1182/blood-2004-06-2098
O'Sullivan, Brian P. ; Linden, Matthew D. ; Frelinger, Andrew L. ; Barnard, Marc R. ; Spencer-Manzon, Michele ; Morris, James E. ; Salem, Raneem O. ; Laposata, Michael ; Michelson, Alan D. / Platelet activation in cystic fibrosis. In: Blood. 2005 ; Vol. 105, No. 12. pp. 4635-4641.
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