Platelet activation by a relapsing fever spirochaete results in enhanced bacterium-platelet interaction via integrin alphaIIbbeta3 activation
Authors
Alugupalli, Kishore R.Michelson, Alan D.
Barnard, Marc R.
Robbins, Douglas
Coburn, Jenifer
Baker, Elizabeth K.
Ginsberg, Mark H.
Schwan, Tom G.
Leong, John M.
Document Type
Journal ArticlePublication Date
2001-01-01Keywords
AnimalsBlood Platelets
Borrelia
CHO Cells
Cricetinae
Culture Media
Humans
Mice
Mice, Inbred C57BL
Mutation
Platelet Activation
Platelet Glycoprotein GPIIb-IIIa Complex
Protein Conformation
Relapsing Fever
Transfection
Hematology
Oncology
Pediatrics
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Show full item recordAbstract
Borrelia hermsii, a spirochaete responsible for relapsing fever in humans, grows to high density in the bloodstream and causes thrombocytopenia. We show here that B. hermsii binds to human platelets. Extended culture in bacteriological medium resulted in both diminished infectivity in vivo and diminished platelet binding in vitro. Platelet binding was promoted by the platelet integrin alphaIIbbeta3: the bacterium bound to purified integrin alphaIIbbeta3, and bacterial binding to platelets was diminished by alphaIIbbeta3 antagonists or by a genetic defect in this integrin. Integrin alphaIIbbeta3 undergoes a conformational change upon platelet activation, and bacteria bound more efficiently to activated rather than resting platelets. Nevertheless, B. hermsii bound at detectable levels to preparations of resting platelets. The bacterium did not recognize a point mutant of alphaIIbbeta3 that cannot acquire an active conformation. Rather, B. hermsii was capable of triggering platelet and integrin alphaIIbbeta3 activation, as indicated by the expression of the platelet activation marker P-selectin and integrin alphaIIbbeta3 in its active conformation. The degree of platelet activation varied depending upon bacterial strain and growth conditions. Prostacyclin I2, an inhibitor of platelet activation, diminished bacterial attachment, indicating that activation enhanced bacterial binding. Thus, B. hermsii signals the host cell to activate a critical receptor for the bacterium, thereby promoting high-level bacterial attachment.Source
Mol Microbiol. 2001 Jan;39(2):330-40. DOI: 10.1046/j.1365-2958.2001.02201.xDOI
10.1046/j.1365-2958.2001.02201.xPermanent Link to this Item
http://hdl.handle.net/20.500.14038/43353PubMed ID
11136454Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1046/j.1365-2958.2001.02201.x
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In vitro testing of fresh and lyophilized reconstituted human and baboon plateletsValeri, C. Robert; Macgregor, Hollace; Barnard, Marc R.; Summaria, L.; Michelson, Alan D.; Ragno, G. (2004-10-01)BACKGROUND: Studies have been performed on human fresh, liquid-preserved, and cryopreserved platelets (PLTs) to assess PLT-adhesive surface receptors, PLT membrane procoagulant activity, PLT aggregation, and thromboxane production. Lyophilization has been developed as a method to preserve PLTs. This study was performed to evaluate these measurements on human and baboon fresh and lyophilized reconstituted PLTs. STUDY DESIGN AND METHODS: In both human and baboon fresh and lyophilized PLTs, aggregation response and PLT production of thromboxane A2 were measured after stimulation, and PLT surface markers P-selectin, glycoprotein (GP) Ib, GPIIb-IIIa, and factor (F) V were measured before and after stimulation. RESULTS: Fresh PLTs responded to the dual agonists arachidonic acid and adenosine diphosphate (ADP) to aggregate and produce thromboxane A2, and in both the PLT surface markers P-selectin and GPIIb-IIIa increased and GPIb decreased after stimulation. Neither human nor baboon lyophilized reconstituted PLTs aggregated to dual agonists, and neither produced thromboxane A2, increased PLT surface markers P-selectin or GPIIb-IIIa, or decreased PLT GPIb after stimulation. Nevertheless, after recalcification the lyophilized reconstituted PLTs accumulated FV to a significantly greater degree than fresh PLTs. CONCLUSIONS: Lyophilized reconstituted PLTs exhibited modification of the PLT membrane that interfered with aggregation and thromboxane production, prevented increases in PLT P-selectin and GPIIb-IIIa and decreases in GPIb after stimulation, and increased FV accumulation after recalcification. The in vitro data suggest that lyophilized PLTs may have reduced in vivo survival. In vivo studies are needed to determine the survival and function of lyophilized PLTs.