Tumor necrosis factor-α-induced leukocyte adhesion and microvessel permeability

Min Zeng, Hong Zhang, Clifford Lowell, Pingnian He

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

The objective of this study was to investigate whether leukocyte adhesion and/or emigration are critical steps in increased microvessel permeability during acute inflammation. To conduct this study, we combined autologous blood perfusion with a single microvessel perfusion technique, which allows microvessel permeability to be measured precisely after the endothelium has interacted with blood-borne stimuli. Experiments were carried out in intact venular microvessels in rat mesenteries. Firm attachment of leukocytes to endothelial cells was induced by intravenous injection of TNF-α (3.5 μg/kg) and resuming autoperfusion in a precannulated microvessel. Leukocyte emigration was facilitated by superfusion of formyl-Met-Leu-Phe-OH. Microvessel permeability was measured as hydraulic conductivity (L p) or the solute permeability coefficient to tetramethylrhodamine isothiocyanate-labeled α-lactalbumin before and after leukocyte adhesion and emigration in individually perfused microvessels. We found that perfusion of a microvessel with TNF-α did not affect basal microvessel permeability, but intravenous injection of TNF-α caused significant leukocyte adhesion. However, the significant leukocyte adhesion and emigration did not cause corresponding increases in either L p or solute permeability. Thus our results suggest that leukocyte adhesion and emigration do not necessarily increase microvessel permeability and the mechanisms that regulate the adhesion process act independently from mechanisms that regulate permeability. In addition, silver staining of endothelial boundaries demonstrated that leukocytes preferentially adhere at the junctions of endothelial cells. The appearance of the silver lines indicates that the TNF-α-induced firm adhesion of leukocyte to microvessel walls did not involve apparent changes in the junctional structure of endothelial cells, which is consistent with the results of permeability measurements.

Original languageEnglish (US)
Pages (from-to)H2420-H2430
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume283
Issue number6 52-6
StatePublished - Dec 1 2002

Fingerprint

Microvessels
Permeability
Leukocytes
Tumor Necrosis Factor-alpha
Emigration and Immigration
Endothelial Cells
Perfusion
Intravenous Injections
methionyl-leucyl-phenylalanine
Lactalbumin
Silver Staining
Mesentery
Silver
Endothelium
Inflammation

All Science Journal Classification (ASJC) codes

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

Cite this

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abstract = "The objective of this study was to investigate whether leukocyte adhesion and/or emigration are critical steps in increased microvessel permeability during acute inflammation. To conduct this study, we combined autologous blood perfusion with a single microvessel perfusion technique, which allows microvessel permeability to be measured precisely after the endothelium has interacted with blood-borne stimuli. Experiments were carried out in intact venular microvessels in rat mesenteries. Firm attachment of leukocytes to endothelial cells was induced by intravenous injection of TNF-α (3.5 μg/kg) and resuming autoperfusion in a precannulated microvessel. Leukocyte emigration was facilitated by superfusion of formyl-Met-Leu-Phe-OH. Microvessel permeability was measured as hydraulic conductivity (L p) or the solute permeability coefficient to tetramethylrhodamine isothiocyanate-labeled α-lactalbumin before and after leukocyte adhesion and emigration in individually perfused microvessels. We found that perfusion of a microvessel with TNF-α did not affect basal microvessel permeability, but intravenous injection of TNF-α caused significant leukocyte adhesion. However, the significant leukocyte adhesion and emigration did not cause corresponding increases in either L p or solute permeability. Thus our results suggest that leukocyte adhesion and emigration do not necessarily increase microvessel permeability and the mechanisms that regulate the adhesion process act independently from mechanisms that regulate permeability. In addition, silver staining of endothelial boundaries demonstrated that leukocytes preferentially adhere at the junctions of endothelial cells. The appearance of the silver lines indicates that the TNF-α-induced firm adhesion of leukocyte to microvessel walls did not involve apparent changes in the junctional structure of endothelial cells, which is consistent with the results of permeability measurements.",
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Tumor necrosis factor-α-induced leukocyte adhesion and microvessel permeability. / Zeng, Min; Zhang, Hong; Lowell, Clifford; He, Pingnian.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 283, No. 6 52-6, 01.12.2002, p. H2420-H2430.

Research output: Contribution to journalArticle

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