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T cell gelatinases mediate basement membrane transmigration in vitro
D Leppert1, E Waubant, R Galardy
1Department of Neurology, University of California at San Francisco 94143, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|May 1, 1995
Summary
Normal human T cells use gelatinases A and B to cross the basal lamina, crucial for tissue entry. Inhibiting these matrix metalloproteinases may treat T cell-mediated autoimmune diseases.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- T cell homing to extravascular sites necessitates crossing the subendothelial basal lamina.
- The basal lamina is a specialized connective tissue anchoring endothelial cells to parenchymal surfaces.
Purpose of the Study:
- To investigate the role of gelatinases A and B in T cell migration across the basal lamina.
- To explore the potential of targeting gelatinases for autoimmune disease treatment.
Main Methods:
- Analysis of gelatinase A and B expression in normal human T cells at mRNA and protein levels.
- In vitro migration assays using a basal lamina equivalent.
- Inhibition studies using GM6001, a matrix metalloproteinase inhibitor.
Main Results:
- Normal human T cells express gelatinases A and B, matrix metalloproteinases targeting collagen types IV and V.
- Gelatinase B is constitutively expressed, while gelatinase A and B expression increases upon T cell activation.
- In vitro T cell migration across the basal lamina is mediated by gelatinase B and blocked by GM6001.
Conclusions:
- Gelatinases A and B are critical for T cell transmigration through the basal lamina.
- Targeting gelatinase function offers a potential therapeutic strategy for T cell-mediated autoimmune diseases.