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Platelet antistaphylococcal responses occur through P2X1 and P2Y12 receptor-induced activation and kinocidin release
Authors
Trier, Darin A.Gank, Kimberly D.
Kupferwasser, Deborah
Young, Nannette Y
French, William J.
Michelson, Alan D.
Kupferwasser, Leon I.
Xiong, Yan Q.
Bayer, Arnold S.
Yeaman, Michael R.
UMass Chan Affiliations
Department of PediatricsDocument Type
Journal ArticlePublication Date
2008-12-01Keywords
AnimalsBlood Platelets
Chemokines
Chromatography, High Pressure Liquid
Platelet Activation
Rabbits
Receptors, Purinergic P2
Receptors, Purinergic P2X
Receptors, Purinergic P2Y12
Staphylococcal Infections
Staphylococcus aureus
Hematology
Oncology
Pediatrics
Metadata
Show full item recordAbstract
Platelets (PLTs) act in antimicrobial host defense by releasing PLT microbicidal proteins (PMPs) or PLT kinocidins (PKs). Receptors mediating staphylocidal efficacy and PMP or PK release versus isogenic PMP-susceptible (ISP479C) and -resistant (ISP479R) Staphylococcus aureus strains were examined in vitro. Isolated PLTs were incubated with ISP479C or ISP479R (PLT/S. aureus ratio range, 1:1 to 10,000:1) in the presence or absence of a panel of PLT inhibitors, including P2X and P2Y receptor antagonists of increasingly narrow specificity, and PLT adhesion receptors (CD41, CD42b, and CD62P). PLT-to-S. aureus exposure ratios of > or = 10:1 yielded significant reductions in the viability of both strains. Results from reversed-phase high-performance liquid chromatography indicated that staphylocidal PLT releasates contained PMPs and PKs. At ratios below 10:1, the PLT antistaphylococcal efficacy relative to the intrinsic S. aureus PMP-susceptible or -resistant phenotype diminished. Apyrase (an agent of ADP degradation), suramin (a general P2 receptor antagonist), pyridoxal 5'-phosphonucleotide derivative (a specific P2X(1) antagonist), and cangrelor (a specific P2Y(12) antagonist) mitigated the PLT staphylocidal response against both strains, correlating with reduced levels of PMP and PK release. Specific inhibition occurred in the presence and absence of homologous plasma. The antagonism of the thromboxane A(2), cyclooxygenase-1/cyclooxygenase-2, or phospholipase C pathway or the hindrance of surface adhesion receptors failed to impede PLT anti-S. aureus responses. These results suggest a multifactorial PLT anti-S. aureus response mechanism involving (i) a PLT-to-S. aureus ratio sufficient for activation; (ii) the ensuing degranulation of PMPs, PKs, ADP, and/or ATP; (iii) the activation of P2X(1)/P2Y(12) receptors on adjacent PLTs; and (iv) the recursive amplification of PMP and PK release from these PLTs.Source
Infect Immun. 2008 Dec;76(12):5706-13. Epub 2008 Sep 29. doi 10.1128/IAI.00935-08. Link to article on publisher's websiteDOI
10.1128/IAI.00935-08Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43306PubMed ID
18824536Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1128/IAI.00935-08