The importance of the interaction between leukocyte integrin Mac-1 and platelet glycoprotein Ib-a for leukocyte recruitment by platelets and for the inflammatory response to vascular injury.

Abstract

OBJECTIVE:

To assess the importance of the interaction between leukocyte integrin Mac-1 (a Mb 2) and platelet glycoprotein (GP) Ib-a for leukocyte recruitment after vascular injury and the effect of the neutralization of the Mac-1-GPIba interaction on cell proliferation and the neointimal hyperplasia triggered by the vascular injury.

METHODS:

A peptide called M2 or anti-M2 antibody was developed to block the Mac-1-GPIba interaction. This peptide was injected and compared to a control-peptide in C57B1/6J mice submitted to vascular injury of the femoral artery with a guide wire. One, five or 28 days after the vascular injury, the femoral arteries were removed for morphometric and immunohistochemical analyses.

RESULTS:

The blocking of the Mac-1-GPIba interaction promoted a statistically significant reduction in the number of leukocytes in the neointimal layer on the first day after the vascular injury (control: 7.9+/-5.0% of the cell total versus anti-M2: 2.0+/-1.6%, p=0.021), as well as determined a statistically significant decrease in leukocyte accumulation in the neointimal layer on days 5 and 28 (control: 42.3+/-12.9% versus anti-M2: 24.6+/-10.8%, p=0.047 and control: 7.9+/-3.0% versus anti-M2: 3.3+/-1.3%, p=0.012; respectively). Cell proliferation in the neointimal layer of the vessel five days post-injury was reduced with the blocking of the Mac-1-GPIba interaction (control: 5.0+/-2.9% of the cell total versus anti-M2: 1.8+/-0.5%; p=0.043), along with a significant decrease in cell proliferation in the vessel neointimal layer 28 days post-injury (control: 3.8+/-1.7% versus anti-M2: 2.0+/-1.2%; p=0.047). The blocking of the Mac-1-GPIba interaction also determined a statistically significant decrease of the intimal thickening 28 days post-injury (control: 10,395+/-3,549 microm(2) versus anti-M2: 4,561+/-4,915 microm(2); p=0.012).

CONCLUSION:

Leukocyte recruitment after a vascular injury depends on the Mac-1-GPIba interaction and the neutralization of this interaction inhibits cell proliferation and neointimal formation.

• Authors: Alexandre C Zago, Daniel I Simon, Yunmei Wang, Masashi Sakuma, Zhiping Chen, Kevin Croce, Valentin Ustinov, Can Shi, Eulógio E Martinez Filho
• Journal: Arquivos brasileiros de cardiologia (Arq Bras Cardiol) Vol. 90 Issue 1 Pg. 54-63 (Jan 2008) ISSN: 1678-4170 [Electronic] Brazil
• PMID: 18317641 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Immunoglobulin G
• Macrophage-1 Antigen
• Peptides
• Platelet Glycoprotein GPIb-IX Complex

Topics

• Animals
• Antibodies, Monoclonal (administration & dosage, immunology)
• Blood Platelets (metabolism)
• Cell Proliferation
• Femoral Artery (injuries, metabolism)
• Immunoglobulin G (administration & dosage)
• Inflammation (metabolism)
• Leukocytes (physiology)
• Macrophage-1 Antigen (analysis, physiology)
• Male
• Mice
• Mice, Inbred C57BL
• Models, Animal
• Peptides (administration & dosage, immunology)
• Platelet Adhesiveness (physiology)
• Platelet Glycoprotein GPIb-IX Complex (drug effects, physiology)
• Rabbits
• Statistics, Nonparametric
• Tunica Intima (immunology, pathology)