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PMID: 2703527 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Disruption of the subendothelial basement membrane during neutrophil diapedesis in an in vitro construct of a blood vessel wall.

The Journal of clinical investigation ·Vol. 83 ·No. 4 ·1989-04-00 ·Pages 1122-36

Huber AR, Weiss SJ

Abstract

To examine the course of physiologic interactions between extravasating neutrophils and the subendothelial basement membrane, a model of the venular vessel wall was constructed by culturing human umbilical vein endothelial cells on a collagen matrix. After 21 d in culture, the endothelial cell monolayer displayed in vivo-like intercellular borders and junctions, deposited a single-layered, continuous basement membrane that was impenetrable to colloidal particles, and supported neutrophil extravasation in a physiologic manner. Using this model, we demonstrate that neutrophil transmigration in a plasma milieu was associated with a significant disruption of the retentive properties of the basement membrane in the absence of discernable morphologic changes. The loss of basement membrane integrity associated with neutrophil diapedesis was not dependent on neutrophil elastase or cathepsin G and was resistant to inhibitors directed against neutrophil collagenase, gelatinase, and heparanase. Despite the fact that this loss in matrix integrity could not be prevented, basement membrane defects were only transiently expressed before they were repaired by the overlying endothelium via a mechanism that required active protein and RNA synthesis. These data indicate that neutrophil extravasation and reversible basement membrane disruption are coordinated events that occur as a consequence of vessel wall transmigration.

MeSH Terms
Basement Membrane/pathology,physiology,ultrastructure Cathepsin G Cathepsins/antagonists & inhibitors Cell Movement Cells, Cultured Endothelium, Vascular/pathology,physiology,ultrastructure Extracellular Matrix/pathology,physiology,ultrastructure Humans Kinetics Lysosomes/enzymology Neutrophils/enzymology,physiology,ultrastructure Pancreatic Elastase/antagonists & inhibitors Permeability Serine Endopeptidases Umbilical Veins
Chemicals
Cathepsins Serine Endopeptidases CTSG protein, human Cathepsin G Pancreatic Elastase
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Huber A R
Department of Internal Medicine, University of Michigan, Ann Arbor 48109.
Weiss S J
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
Published
1989-04-00
Pages
1122-36
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC303798
Subset
IM
Grants
NIAID NIH HHS · AI-23876 · United States
NHLBI NIH HHS · HL-28024 · United States
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