Mechanisms of poly-N-acetyl glucosamine polymer-mediated hemostasis: platelet interactions.
BACKGROUND
Investigations were performed to determine whether poly-N-acetyl glucosamine (p-GlcNAc) induces hemostasis by the activation of platelets.


METHODS
Platelets were isolated from human blood, fixed in the presence poly-N-acetyl glucosamine fibers, and visualized with scanning electron microscopy. Platelet activation surface markers were measured by fluorescence multiphoton microscopy. Platelet aggregation in the presence of p-GlcNAc fibers and integrin receptor blockers was measured.


RESULTS
Scanning electron microscopy indicated that contact of platelets with poly-N-acetyl glucosamine fibers resulted in platelet activation. Fluorescent microscopy showed that contact of platelets with the marine polymer increased intracellular levels of free calcium and resulted in surface exposure of platelet phosphatidylserine, P selectin, and the alphaIIbbeta3 integrin. Antibody inhibitors of the platelet alphaIIbbeta3 integrin inhibited p-GlcNAc to stimulate fibrin polymerization.


CONCLUSIONS
Poly-N-acetyl glucosamine fiber material promotes hemostasis by the activation of platelets.
Department Surgery, VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical Schools, Boston, MA, USA.
Hemant S
HS
Thatte
Sofija
S
Zagarins
Shukri F
SF
Khuri
Thomas H
TH
Fischer
D000117:Acetylglucosamine / Q000737:chemistry / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000648:ultrastructure; D002118:Calcium / Q000502:physiology; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D048271:Chitosan; D004353:Drug Evaluation, Preclinical; D005337:Fibrin / Q000187:drug effects; D006488:Hemostasis, Surgical / Q000379:methods; D006490:Hemostatics / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D039421:Integrin alpha2; D039482:Integrin alpha5 / Q000187:drug effects; D039503:Integrin alpha6 / Q000187:drug effects; D039661:Integrin beta3 / Q000187:drug effects; D007424:Intracellular Fluid / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D036641:Microscopy, Fluorescence, Multiphoton; D019007:P-Selectin / Q000187:drug effects; D010718:Phosphatidylserines / Q000502:physiology; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology; D010973:Platelet Adhesiveness / Q000187:drug effects; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000187:drug effects; D040201:Platelet Membrane Glycoprotein IIb / Q000187:drug effects; D013053:Spectrophotometry; D013997:Time Factors
D006490:Hemostatics; C056564:ITGA2B protein, human; D039421:Integrin alpha2; D039482:Integrin alpha5; D039503:Integrin alpha6; D039661:Integrin beta3; D008562:Membrane Glycoproteins; D019007:P-Selectin; D010718:Phosphatidylserines; D019038:Platelet Glycoprotein GPIb-IX Complex; D040201:Platelet Membrane Glycoprotein IIb; C113831:poly-N-acetyl glucosamine; D002686:Chitin; D005337:Fibrin; D048271:Chitosan; D002118:Calcium; D000117:Acetylglucosamine