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Divalent cations and the protein surface co-ordinate the intensity of human platelet adhesion and P-selectin surface expression
Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.ORCID iD: 0000-0003-3184-0427
Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
2002 (English)In: Blood Coagulation and Fibrinolysis, ISSN 0957-5235, E-ISSN 1473-5733, Vol. 13, no 5, 407-416 p.Article in journal (Refereed) Published
Abstract [en]

At sites of blood vessel injury, platelets adhere to exposed vessel components, such as collagen, or immobilized fibrinogen derived from plasma or activated platelets. The divalent cations Mg2+ and Ca2+ are essential for platelet adhesion and activation, but Mg2+ can also inhibit platelet activation. The present study evaluates, by an enzymatic method, the effects of various divalent cations on the adhesion of isolated human platelets to collagen, fibrinogen, albumin or plastic in vitro. By enzyme-linked immunosorbent assay, platelet surface expression of P-selectin was measured to estimate the state of activation on adherence. Mg2+ increased platelet adhesion exclusively to collagen and fibrinogen at physiologically relevant concentrations. At higher concentrations, the adhesion declined. Ca2+ induced a weak adhesion only to fibrinogen at physiological doses and a peak of increased adhesion to all protein-coated surfaces at 10 mmol/l. Mn2+ elicited dose-dependent adhesion only to collagen and fibrinogen. Zn2+, Ni2+ and Cu2+ increased the adhesion of platelets independently of the surface. Ca2+ dose-dependently inhibited adhesion elicited by Mg2+ to collagen and fibrinogen. No other combination of divalent cations elicited such an effect. Mg2+-dependent platelet adhesion to collagen and Ca2+-dependent adhesion to fibrinogen increased P-selectin expression. Thus, the present study shows that the outcome of the platelet adhesion depends on the surface and the access of divalent cations, which co-ordinate the intensity of platelet adhesion and P-selectin surface expression.

Place, publisher, year, edition, pages
2002. Vol. 13, no 5, 407-416 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-26773DOI: 10.1097/00001721-200207000-00005Local ID: 11377OAI: oai:DiVA.org:liu-26773DiVA: diva2:247323
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2013-09-03Bibliographically approved
In thesis
1. Platelet adhesion and P-selectin surface expression
Open this publication in new window or tab >>Platelet adhesion and P-selectin surface expression
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Upon injury in a blood vessel, platelets become activated and adbere to prevent blood loss. Activated platelets express adhesion molecules on their surface that also make leukocytes adhere to the injury. One such molecule, which also is expressed on endothelium, is the glycoprotein P-selectin. The present studies were focused on how soluble factors and surfaces can affect P-selectin surface expression on human platelets.

This thesis presents an enzyme-linked immunosorbent assay (ELISA) application to study platelet expression and release of P-selectin. The well-known platelet activators collagen, epinephrine, ADP, ristocetin, PMA, and thrombin induced surface expression of P-selectin with different potency and time-dependency in vitro. One of the most powerful platelet activators, thrombin, rapidly mediated both surface expression and release. The surface expression decreased after a short peak upon maximal thrombin-activation. The protein kinase C activator PMA induced surface expression equivalently to thrombin but the release of Pselectin was less as compared to thrombin. Nitric oxide (NO) donors, which mimic a vessel wall mechanism to inhibit platelet activation, decreased expression and release of P-selectin upon activation. Adenosine, another agent that is produced in vivo, acted in concert with NO and totally inhibited P-selectin expression induced by thrombin. NO and adenosine act by increasing the second messengers cGMP and cAMP, respectively.

The effects of an infusion of nicotine on platelet P-selectin expression were studied in nicotine users with normal and impaired renal function. After a peak directly after infusion, the plasma concentration of nicotine declined towards the basal level and the level of NO-products was lower as compared to baseline 2 h after infusion. At the same time, P-selectin expression induced by weak activators, but not by thrombin, increased in both groups. A transient and weak inhibition of collagen-induced platelet aggregation was observed directly after infusion. Studies in vitro showed that nicotine per se inhibits P-selectin expression. Thus, nicotine appears to initially inhibit and then increase platelet activation in vivo.

The adhesion of platelets to surfaces that can be exposed upon vessel wall injury and the subsequent expression of P-selectin were found to be dependent on divalent cations. Mg2+ dose-dependently increased platelet adhesion to both collagen and fibrinogen in the physiological range, but supraphysiological concentrations decreased the adhesion to fibrinogen. Ca2+ did only increase platelet adhesion to fibrinogen. Platelet adhesion to collagen caused more expression of P-selectin than adhesion to fibrinogen. Thus, the surface and the access of divalent cations regulate platelet adhesion and P-selectin surface expression.

In summary, multiple factors rep1late and affect platelet adhesion and P-selectin surface expression. The methods presented in this thesis are suitable for studies to further understand and make pharmacological modulation possible of these complex mechanisms and consequences.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2000. 86 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 641
Keyword
divalent cations, ELISA, nicotine, nitric oxide, platelet adhesion, P-selectin
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-27555 (URN)12216 (Local ID)91-7219-742-0 (ISBN)12216 (Archive number)12216 (OAI)
Public defence
2000-10-06, Berzeliussalen, Universitetssjukhuset, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2013-09-03Bibliographically approved

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Whiss, Per AAndersson, Rolf

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