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[Increase in pulmonary vascular permeability caused by increased expression of Mac-1 on the surface of
1Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Abstract:
We studied the expression of adhesion molecules on the surface of human polymorphonuclear leukocytes (PMNs). The effects of mechanical stimulation were measured with a flow cytometer and pulmonary vascular injury due to accumulation of PMNs in the lungs was assessed by a gravimetric method. The accumulation of PMNs in the lungs was studied by measuring the amount of myeloperoxidase. PMNs were stimulated by gentle agitation in a glass container for 10 s. Mac-1 (CD11b/CD18) was upregulated on the surface of PMNs that were mechanically stimulated. When unstimulated PMNs were exposed to isolated rat lungs, the filtration coefficient did not change from that under baseline conditions. However, when mechanically stimulated PMNs were exposed to isolated rat lungs, the filtration coefficient was about 5 times higher than that measured at baseline. When mechanically stimulated PMNs treated with anti-CD18 antibody were used, the increase in the filtration coefficient was completely blocked. The assay of myeloperoxidase revealed that PMNs stuck to isolated rat lungs only after stimulated PMNs were added. We conclude that when the adhesiveness of PMNs is increased by mechanical stimulation, these cells adhere to pulmonary vessels and increase pulmonary vascular permeability.
Insights
Mechanical stimulation increases the adhesiveness of polymorphonuclear leukocytes (PMNs), causing them to stick to lung vessels. This leads to increased pulmonary vascular permeability and injury.
Area of Science:
- Immunology
- Cell Biology
- Pulmonary Medicine
Context:
- Polymorphonuclear leukocytes (PMNs) play a critical role in inflammatory responses.
- Mechanical forces can influence cellular behavior and immune cell function.
- Pulmonary vascular injury is a significant clinical concern.
Purpose:
- To investigate the effect of mechanical stimulation on PMN adhesion molecule expression.
- To determine the impact of mechanically stimulated PMNs on pulmonary vascular permeability.
- To elucidate the role of Mac-1 (CD11b/CD18) in PMN-induced lung injury.
Summary:
- Mechanical stimulation of human PMNs for 10 seconds upregulated Mac-1 (CD11b/CD18) expression.
- Mechanically stimulated PMNs significantly increased pulmonary vascular filtration coefficient in isolated rat lungs.
- Blocking CD18 with an antibody completely prevented this increase, indicating its crucial role.
Impact:
- Mechanical forces can prime PMNs for adhesion and subsequent lung injury.
- Targeting CD18 may offer a therapeutic strategy to mitigate PMN-mediated pulmonary vascular damage.
- This study highlights a novel mechanism linking mechanical stress to inflammatory cell dysfunction in the lungs.