Leukocyte-platelet aggregate adhesion and vascular permeability in intact microvessels: Role of activated endothelial cells

Pingnian He, Hong Zhang, Longkun Zhu, Yanyan Jiang, Xueping Zhou

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Leukocyte-platelet aggregation and aggregate adhesion have been indicated as biomarkers of the severity of tissue injury during inflammation or ischemic reperfusion. The objective of this study is to investigate the mechanisms of the aggregate adhesion and quantitatively evaluate its relationship with microvessel permeability. A combined autologous blood perfusion with single microvessel perfusion technique was employed in rat mesenteric venular microvessels. The aggregate adhesion was induced by systemic application of TNF-α plus local application of platelet-activating factor (PAF). Changes in permeability were determined by measurements of hydraulic conductivity (L p) before and after aggregate adhesion in the same individually perfused microvessels. The compositions of the adherent aggregates were identified with fluorescent labeling and confocal imaging. In contrast to leukocyte adhesion as single cells resulting in no increase in microvessel permeability, aggregate adhesion induced prolonged increases in microvessel L p (6.1 ± 0.9 times the control, n = 9) indicated by the initial L p measurements after 3 h of blood perfusion, which is distinct from the transient L p increase caused by PAF-induced endothelial activation in the absence of blood. Isoproteronol (Iso) attenuated aggregate adhesion-mediated L p increases if applied after autologous blood perfusion and prevented the aggregate adhesion if the initial endothelial activation is inhibited by applying Iso before PAF administration but showed less effect on single leukocyte adhesion. This study demonstrated that leukocyte-platelet aggregate adhesion via a mechanism different from that of single leukocyte adhesion caused a prolonged increase in microvessel permeability. Our results also indicate that the initial activation of endothelial cells by PAF plays a crucial role in the initiation of leukocyte-platelet aggregate adhesion.

Original languageEnglish (US)
Pages (from-to)H591-H599
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume291
Issue number2
DOIs
StatePublished - Aug 10 2006

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Capillary Permeability
Microvessels
Leukocytes
Blood Platelets
Endothelial Cells
Platelet Activating Factor
Permeability
Perfusion
Platelet Aggregation
Reperfusion
Biomarkers
Inflammation
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

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title = "Leukocyte-platelet aggregate adhesion and vascular permeability in intact microvessels: Role of activated endothelial cells",
abstract = "Leukocyte-platelet aggregation and aggregate adhesion have been indicated as biomarkers of the severity of tissue injury during inflammation or ischemic reperfusion. The objective of this study is to investigate the mechanisms of the aggregate adhesion and quantitatively evaluate its relationship with microvessel permeability. A combined autologous blood perfusion with single microvessel perfusion technique was employed in rat mesenteric venular microvessels. The aggregate adhesion was induced by systemic application of TNF-α plus local application of platelet-activating factor (PAF). Changes in permeability were determined by measurements of hydraulic conductivity (L p) before and after aggregate adhesion in the same individually perfused microvessels. The compositions of the adherent aggregates were identified with fluorescent labeling and confocal imaging. In contrast to leukocyte adhesion as single cells resulting in no increase in microvessel permeability, aggregate adhesion induced prolonged increases in microvessel L p (6.1 ± 0.9 times the control, n = 9) indicated by the initial L p measurements after 3 h of blood perfusion, which is distinct from the transient L p increase caused by PAF-induced endothelial activation in the absence of blood. Isoproteronol (Iso) attenuated aggregate adhesion-mediated L p increases if applied after autologous blood perfusion and prevented the aggregate adhesion if the initial endothelial activation is inhibited by applying Iso before PAF administration but showed less effect on single leukocyte adhesion. This study demonstrated that leukocyte-platelet aggregate adhesion via a mechanism different from that of single leukocyte adhesion caused a prolonged increase in microvessel permeability. Our results also indicate that the initial activation of endothelial cells by PAF plays a crucial role in the initiation of leukocyte-platelet aggregate adhesion.",
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Leukocyte-platelet aggregate adhesion and vascular permeability in intact microvessels : Role of activated endothelial cells. / He, Pingnian; Zhang, Hong; Zhu, Longkun; Jiang, Yanyan; Zhou, Xueping.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 291, No. 2, 10.08.2006, p. H591-H599.

Research output: Contribution to journalArticle

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AU - He, Pingnian

AU - Zhang, Hong

AU - Zhu, Longkun

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AU - Zhou, Xueping

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