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Rapid and Robust Analysis of Cellular and Molecular Polarization Induced by Chemokine Signaling
Published on: December 12, 2014
Uncoupling protein-2 negatively regulates polymorphonuclear leukocytes chemotaxis via modulating [Ca2+] influx.
Dan-Qing Liu1, Ya-Lan Guo, Zhen Bian
1Chen-Yu Zhang, PhD, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, Peoples Republic of China.
Arteriosclerosis, Thrombosis, and Vascular Biology
|December 25, 2009
Summary
Uncoupling protein 2 (UCP2) inhibits polymorphonuclear leukocyte (PMN) migration. Deleting UCP2 enhances PMN chemotaxis, suggesting UCP2 acts as a brake on inflammatory cell movement.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Uncoupling protein 2 (UCP2) is known to negatively regulate inflammatory responses in leukocytes.
- The precise mechanisms by which UCP2 influences leukocyte inflammatory responses, particularly cell migration, remain incompletely understood.
Purpose of the Study:
- This study aimed to investigate the specific role of UCP2 in polymorphonuclear leukocyte (PMN) chemotaxis.
- We sought to elucidate the molecular mechanisms underlying UCP2's effect on PMN migration.
Main Methods:
- PMN chemotaxis was assessed in vivo using a zymosan-induced murine peritonitis model and in vitro using transmigration assays with isolated PMN stimulated by N-formyl-methionyl-leucyl-phenylalanine (fMLP).
- UCP2 expression levels were analyzed in migrated versus non-migrated PMN.
- Additionally, PMN chemotaxis was evaluated in streptozotocin-induced diabetic mice with enhanced UCP2 expression.
- Changes in surface expression of adhesion molecules (CD11b/CD18 and CD11a/CD18) and fMLP-triggered intracellular calcium mobilization were compared between UCP2-deficient and wild-type PMN.
Main Results:
- UCP2-deficient (UCP2(-/-)) mice exhibited significantly increased PMN migration in peritoneal lavage compared to wild-type littermates.
- In vitro assays confirmed that UCP2(-/-) PMN migrated faster than wild-type PMN in response to fMLP.
- Migrated PMN showed decreased UCP2 expression, supporting an inhibitory role for UCP2 in transmigration.
- Conversely, enhanced UCP2 expression in diabetic mice correlated with reduced PMN chemotaxis.
- UCP2(-/-) PMN displayed enhanced upregulation of CD11b/CD18 and CD11a/CD18 and exhibited quicker, larger intracellular calcium mobilization upon fMLP stimulation compared to UCP2(+/+) PMN.
Conclusions:
- The study demonstrates that UCP2 functions as an inhibitory regulator, or 'brake,' controlling PMN chemotaxis.
- The findings suggest that UCP2 modulates PMN chemotaxis potentially by influencing intracellular calcium influx and adhesion molecule expression.
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