PECAM-1 and gelatinase B coexist in vascular cuffs of multiple sclerosis lesions

Area of Science:

• Neuroimmunology
• Molecular Biology
• Pathology

Background:

• Matrix metalloproteinase gelatinase B (MMP-9) and PECAM-1 are implicated in leukocyte infiltration in multiple sclerosis (MS).
• The functional relationship between gelatinase B and PECAM-1 in MS pathogenesis remains unexplored.

Purpose of the Study:

• To investigate the expression and co-localization of gelatinase B and PECAM-1 in post-mortem MS brains.
• To determine if gelatinase B or matrilysin-1 (MMP-7) cleaves PECAM-1, potentially explaining elevated soluble PECAM-1 in MS patients.

Main Methods:

• Immunohistochemistry on post-mortem MS brain tissue.
• In vitro proteolytic cleavage assays using Western blot and flow cytometry.
• Analysis of human THP-1 monocyte and soluble recombinant PECAM-1.

Main Results:

• PECAM-1 is constitutively expressed on brain endothelial cells and upregulated on macrophages in active MS lesions, co-localizing with gelatinase B.
• In vitro studies demonstrated that gelatinase B and matrilysin-1 do not cleave human PECAM-1.
• Soluble recombinant PECAM-1 and monocyte-bound PECAM-1 were resistant to proteolytic degradation by these MMPs.

Conclusions:

• PECAM-1 and gelatinase B expression is upregulated and co-localized in active MS lesions.
• Gelatinase B and matrilysin-1 do not directly cleave PECAM-1 in vitro.
• PECAM-1 and gelatinase B may function synergistically in mononuclear cell transmigration across the blood-brain barrier in MS.