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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #329143

Research Project: Molecular, Cellular, and Regulatory Aspects of Nutrition During Development

Location: Children's Nutrition Research Center

Title: Intergrin-dependent neutrophil migration in the injured mouse cornea

item HANLON, SD - University Of Houston
item SMITH, CW - Children'S Nutrition Research Center (CNRC)
item SAUTER, MN - University Of Houston
item BURNS, AR - University Of Houston

Submitted to: Experimental Eye Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/24/2014
Publication Date: 3/20/2014
Citation: Hanlon, S., Smith, C., Sauter, M., Burns, A. 2014. Intergrin-dependent neutrophil migration in the injured mouse cornea. Experimental Eye Research. 120:61-70.

Interpretive Summary: This study in young mice on a normal diet focused on the ability of a type of white blood cell called a neutrophil to leave the blood and crawl through the cornea, clear surface of the eye. This ability is important since it promotes healing of wounds and also helps protect the eye against infection. The experiments show for the first time that the neutrophils as they crawl hold on to a specialized tissue cell in the cornea called a keratocyte. This allows these important white blood cells to reach areas that may be wounded. This work is important because of recent findings that healing of the corneal wounds is delayed in mice fed a high fat diet known to alter the function of these neutrophils.

Technical Abstract: As an early responder to an inflammatory stimulus, neutrophils 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, neutrophils recruited from the peripheral limbal vasculature migrate into the avascular corneal stroma. In vitro studies suggest neutrophils 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 neutrophils make extensive surface contact not only with collagen fibrils in the extracellular matrix, 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-extracellular matrix) 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 neutrophil interactions with keratocytes and other stromal components in the living eye. The relative contribution of Beta1, Beta2 and Beta3 integrins to neutrophil locomotion in the inflamed mouse cornea was investigated using blocking antibodies against the respective integrins. Of the 3 integrin families (Beta1, Beta2 and Beta3) investigated for their potential role in neutrophil migration, only Beta1 antibody blockade produced a significant, but partial, reduction in neutrophil motility. The preferential migration of neutrophils along the keratocyte network was not affected by integrin blockade. Hence, the dominant mechanism for neutrophil motility within the corneal stroma appears to be integrin-independent as does the restriction of neutrophil migration paths to the keratocyte network.