Integrin-dependent neutrophil migration in the injured mouse cornea
| Autor: | C. Wayne Smith, Alan R. Burns, Marika N. Sauter, Samuel D Hanlon |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Integrins
Stromal cell Neutrophils Corneal Stroma Integrin Motility Corneal Keratocytes Biology Wounds Nonpenetrating Corneal inflammation Article Extracellular matrix Mice Cellular and Molecular Neuroscience Eye Injuries Cornea medicine Animals Antibodies Blocking Integrin binding Keratitis Microscopy Confocal Integrin beta1 Integrin beta3 Sensory Systems Extravasation Cell biology Mice Inbred C57BL Chemotaxis Leukocyte Ophthalmology medicine.anatomical_structure CD18 Antigens Immunology biology.protein Female sense organs Corneal Injuries |
| Zdroj: | Experimental Eye Research. 120:61-70 |
| ISSN: | 0014-4835 |
| DOI: | 10.1016/j.exer.2014.01.004 |
| Popis: | As an early responder to an inflammatory stimulus, neutrophils (PMNs) must exit the vasculature and migrate through the extravascular tissue to the site of insult, which is often remote from the point of extravasation. Following a central epithelial corneal abrasion, PMNs recruited from the peripheral limbal vasculature migrate into the avascular corneal stroma. In vitro studies suggest PMN locomotion over 2-D surfaces is dependent on integrin binding while migration within 3-D matrices can be integrin-independent. Electron micrographs of injured mouse corneas show migrating PMNs make extensive surface contact not only with collagen fibrils in the extracellular matrix (ECM), but also keratocytes. Evidence supporting involvement of integrins in corneal inflammation has prompted research and development of integrin blocking agents for use as anti-inflammatory therapies. However, the role of integrin binding (cell–cell; cell–ECM) during stromal migration in the inflamed cornea has previously not been clearly defined. In this study in vivo time lapse imaging sequences provided the means to quantify cell motility while observing PMN interactions with keratocytes and other stromal components in the living eye. The relative contribution of β1, β2 and β3 integrins to PMN locomotion in the inflamed mouse cornea was investigated using blocking antibodies against the respective integrins. Of the 3 integrin families (β1, β2 and β3) investigated for their potential role in PMN migration, only β1 antibody blockade produced a significant, but partial, reduction in PMN motility. The preferential migration of PMNs along the keratocyte network was not affected by integrin blockade. Hence, the dominant mechanism for PMN motility within the corneal stroma appears to be integrin-independent as does the restriction of PMN migration paths to the keratocyte network. |
| Databáze: | OpenAIRE |
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