Fluorescent labeling of endogenous platelets for intravital microscopy: Effects on platelet function

Microcirculation. 2018 Aug;25(6):e12457. doi: 10.1111/micc.12457. Epub 2018 May 30.

Abstract

Objective: Monitoring endogenous platelets during intravital microscopy often involves two approaches: fluorescently labeled antibodies or genetic models of platelet-specific fluorescent protein expression. Due to limited data available on platelet functional changes induced by these methods, we compared functional effects of these methods on platelets.

Methods: Platelet aggregation to collagen and thrombin, and collagen matrix-mediated platelet adhesion/aggregation under flow were tested. We assessed platelets from mice expressing EYFP on platelets (Cre(+)), littermate controls (Cre(-)), C57BL/6 mice, and platelets from vehicle control and x-488 treatment. We utilized intravital microscopy to monitor platelets in vivo using Cre(+) mice and x-488 treatment.

Results: Both genetic and antibody-based approaches yielded substantial platelet-specific fluorescence. Platelets from Cre(+) and Cre(-) mice behaved similarly in aggregation and adhesion/aggregation under flow. However, they exhibited significantly enhanced aggregation and higher adhesion/aggregation as compared to platelets from C57BL/6 mice. Compared to vehicle control, x-488 platelet labeling did not induce significant functional changes in vitro. Both methods of platelet labeling provided satisfactory platelet detectability in vivo.

Conclusions: x-488 antibody labeling of platelets induced less alteration of platelet function than genetic approaches under our experimental conditions and seems more suitable for monitoring of endogenous platelets.

Keywords: aggregation and adhesion; fluorescent labeling; intravital microscopy; platelet; shear stress.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Blood Platelets / cytology*
  • Blood Platelets / drug effects
  • Fluorescent Dyes / pharmacology*
  • Intravital Microscopy / methods*
  • Mice
  • Platelet Activation / drug effects
  • Staining and Labeling / methods
  • Staining and Labeling / standards

Substances

  • Antibodies
  • Fluorescent Dyes