Related Experiment Video
Updated: Sep 29, 2026
Analysis of Physiologic E-Selectin-Mediated Leukocyte Rolling on Microvascular Endothelium
Published on: February 10, 2009
L-selectin is required for fMLP- but not C5a-induced margination of neutrophils in pulmonary circulation
Timothy S Olson1, Kai Singbartl, Klaus Ley
1Department of Molecular Physiology and Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
Abstract:
To study the role of L-selectin in neutrophil (PMN) margination and sequestration in the pulmonary microcirculation, maximally active concentrations of C5a (900 pmol/g) and N-formylmethionyl-leucyl-phenylalanine (fMLP; 0.34 pmol/g) were injected into the jugular vein of wild-type or L-selectin-deficient C57BL/6 mice. In wild-type mice administered C5a or fMLP, 92 +/- 1% and 34 +/- 9%, respectively, of peripheral blood PMN were trapped mostly in the pulmonary circulation as determined by immunohistochemistry and myeloperoxidase activity. In wild-type mice treated with F(ab')(2) fragments of the L-selectin monoclonal antibody MEL-14 or in L-selectin-deficient mice, C5a-induced neutropenia was not significantly reduced, but the decrease in peripheral PMN in response to fMLP was completely abolished, indicating that L-selectin is necessary for fMLP- but not C5a-induced pulmonary margination. Immunostained lung sections of fMLP- or C5a-treated mice showed sequestered neutrophils in alveolar capillaries with no evidence of neutrophil aggregates. We conclude that chemoattractant-induced PMN margination in the pulmonary circulation can occur by two separate mechanisms, one of which requires L-selectin.
Insights
L-selectin is crucial for fMLP-induced neutrophil sequestration in lung capillaries, but not for C5a-induced margination. This reveals distinct mechanisms controlling neutrophil migration in pulmonary circulation.
Area of Science:
- Immunology
- Pulmonary Circulation
- Cellular Adhesion Molecules
Background:
- Neutrophil margination and sequestration are critical inflammatory processes.
- L-selectin plays a role in leukocyte trafficking.
- Pulmonary microcirculation is a key site for immune cell interactions.
Purpose of the Study:
- To investigate the role of L-selectin in neutrophil margination and sequestration in the pulmonary microcirculation.
- To differentiate the mechanisms of L-selectin-dependent and -independent neutrophil recruitment.
Main Methods:
- Utilized wild-type and L-selectin-deficient mice.
- Administered chemoattractants C5a and N-formylmethionyl-leucyl-phenylalanine (fMLP).
- Assessed neutrophil sequestration using immunohistochemistry and myeloperoxidase activity.
Main Results:
- C5a and fMLP caused significant neutrophil sequestration in wild-type mice.
- L-selectin deficiency or blockade abolished fMLP-induced, but not C5a-induced, neutrophil sequestration.
- Neutrophils were sequestered in alveolar capillaries without aggregation.
Conclusions:
- L-selectin is essential for fMLP-induced neutrophil margination in the pulmonary circulation.
- C5a-induced neutrophil margination occurs via an L-selectin-independent pathway.
- Chemoattractant-induced neutrophil recruitment in the lungs involves at least two distinct mechanisms.
More Related Videos
11:22Quantitative In vitro Assay to Measure Neutrophil Adhesion to Activated Primary Human Microvascular Endothelial Cells under Static Conditions
Published on: August 23, 2013
12:55A Microphysiological System to Study Leukocyte-Endothelial Cell Interaction during Inflammation
Published on: December 9, 2021
Related Concept Videos
01:39Mechanism of Filopodia Formation
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
01:17Intracellular Signaling Affects Focal Adhesions
Some...
01:25Selectins
01:26Acute Inflammation II: Cellular Phase