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Clin Cardiol J Volume 1 | Issue 1

December 04-05, 2017 Dallas, USA

International Conference on

Heart Congress, Vascular Biology and Surgeon’s Meeting

Endothelial intracellular molecule

LSP1

regulates the chemotactic directionality of

extravascular migrating neutrophils

Liu Lixin

University of Saskatchewan, Canada

T

he recruitment of leukocytes from the flowing bloodstream into inflamed tissue is of key importance in

inflammation. This recruitment is characterized as the initial tethering and rolling of leukocytes along the

endothelium, followed by leukocyte activation and firm adhesion to the endothelium, leukocyte transmigration

across the endothelium(diapedesis), and chemotacticmigration of emigrated leukocytes toward the site of infection

or injury (chemotaxis) in tissue. The role of intracellular signaling molecules in leukocytes and endothelial cells

involved in leukocyte recruitment is investigated in the microvasculature

in vivo

.

LSP1

(leukocyte-specific

protein 1), an F-actin-binding, intracellular phosphoprotein, is expressed in leukocytes and endothelial cells with

different intracellular localization pattern. In endothelial cells,

LSP1

is mainly expressed in the nucleus with

small proportion as cytosolic and cytoskeletal protein. The role of endothelial

LSP1

in neutrophil recruitment

is investigated and endothelial

LSP1

-regulated mechanism for extravascular neutrophil chemotaxis is revealed

in our study. Using intravital microscopy in

LSP1

-deficient and

LSP1

-chimeric mice, we show that endothelial

LSP1

plays a permissive role in controlling neutrophil transendothelial migration during neutrophil recruitment

and regulates extravascular migration directionality but not the migration velocity of emigrated neutrophils. We

found that the expression of

α

6

β

1 integrins on the emigrated neutrophils was blunted when

LSP1

was deficient

in the endothelium of LSP1-deficient or chimeric mice, and that neutrophil

α

6

β

1 integrin expression dictated the

directionality of emigrated neutrophils

in vivo

and

in vitro

.

LSP1

-deficiency or

LSP1

-targeted siRNA silencing

in endothelial cells reduced endothelial adhesion molecule PECAM-1 expression through GATA-2-dependent

mechanism.

LSP1

overexpression in endothelial cells has unregulated endothelial PECAM-1 expression. It

was the reduced endothelial PECAM-1 expression in

LSP1

-deficient endothelium that down-regulated

α

6

β

1

integrin expression on the transmigrating neutrophils and that, through PECAM-1-sensitive, down-regulated

α

6

β

1 integrin expression, mitigated the migration directionality of transmigrated neutrophils in tissue. Thus,

endothelial

LSP1

regulates vascular PECAM-1-sensitive and neutrophil integrin

α

6

β

1 dependent directionality

of extravascular neutrophil migration in inflamed tissue during neutrophil recruitment.

Biography

Liu Lixin had research training with Dr. Dirk Roos (CLB, The Netherlands) and completed his PhD study with Dr. Per Venge at Uppsala University (Sweden).

In Europe, he has studied the regulatory mechanisms of granulocyte transmigration across epithelial cell monolayer. Thereafter, as a Post-doctoral Fellow, he has

joined the lab of Dr. Paul Kubes in the University of Calgary, in Alberta, Canada, where he became experienced in the techniques of intravital microscopy and

started to explore the role of intracellular protein molecules in neutrophil transendothelial migration and chemotaxis. In late 2006, he has joined the faculty in the

University of Saskatchewan (Saskatchewan, Canada) and currently he is Associate Professor in Pharmacology. Using intravital microscopy and other imaging

techniques and biochemical and cell biological approaches, his lab is now investigating the role of intracellular signaling molecules in neutrophil-endothelial

cell interactions, with current research interests in the signaling mechanisms of

LSP1

(leukocyte-specific protein 1) and PI3K (phosphoinositide 3-kinases) in

neutrophil recruitment during inflammation.

lixin.liu@usask.ca