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Receptor-mediated interactions of po...

Jadhav, Sameer R.

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Receptor-mediated interactions of polymorphonuclear leukocytes with colon carcinoma cells and selectin substrates under shear.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Receptor-mediated interactions of polymorphonuclear leukocytes with colon carcinoma cells and selectin substrates under shear./
Author:	Jadhav, Sameer R.
Description:	112 p.
Notes:	Source: Dissertation Abstracts International, Volume: 65-12, Section: B, page: 6511.
Contained By:	Dissertation Abstracts International65-12B.
Subject:	Engineering, Chemical. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3155627
ISBN:	0496163493

Receptor-mediated interactions of polymorphonuclear leukocytes with colon carcinoma cells and selectin substrates under shear.
Jadhav, Sameer R.

Receptor-mediated interactions of polymorphonuclear leukocytes with colon carcinoma cells and selectin substrates under shear. - 112 p.

Source: Dissertation Abstracts International, Volume: 65-12, Section: B, page: 6511.

Thesis (Ph.D.)--The Johns Hopkins University, 2005.

Receptor-mediated cell adhesion plays a pivotal role in diverse biological processes that occur in the vasculature including inflammation and cancer metastasis. For instance, a critical step in polymorphonuclear leukocyte (PMN) recruitment to sites of inflammation/infection is their adhesion to the activated endothelium. Also, new evidence suggests that the metastatic spread of certain types of cancers may be enhanced by PMN-tumor cell adhesive interactions. Since these cell-cell adhesive interactions take place in the fluid mechanical environment of the vasculature, it is important to characterize the molecular mechanisms mediating cell adhesion under physiologically relevant flow conditions. Therefore, we examined the effect of hydrodynamic shear on the adhesive interactions of PMNs with carcinoma cells and selectin substrates using experimental and computational methods.

ISBN: 0496163493Subjects--Topical Terms:

1018531
Engineering, Chemical.

Receptor-mediated interactions of polymorphonuclear leukocytes with colon carcinoma cells and selectin substrates under shear.
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100 1 $a Jadhav, Sameer R. $3 1905691
245 1 0 $a Receptor-mediated interactions of polymorphonuclear leukocytes with colon carcinoma cells and selectin substrates under shear.
300 $a 112 p.
500 $a Source: Dissertation Abstracts International, Volume: 65-12, Section: B, page: 6511.
500 $a Adviser: Konstantinos Konstantopoulos.
502 $a Thesis (Ph.D.)--The Johns Hopkins University, 2005.
520 $a Receptor-mediated cell adhesion plays a pivotal role in diverse biological processes that occur in the vasculature including inflammation and cancer metastasis. For instance, a critical step in polymorphonuclear leukocyte (PMN) recruitment to sites of inflammation/infection is their adhesion to the activated endothelium. Also, new evidence suggests that the metastatic spread of certain types of cancers may be enhanced by PMN-tumor cell adhesive interactions. Since these cell-cell adhesive interactions take place in the fluid mechanical environment of the vasculature, it is important to characterize the molecular mechanisms mediating cell adhesion under physiologically relevant flow conditions. Therefore, we examined the effect of hydrodynamic shear on the adhesive interactions of PMNs with carcinoma cells and selectin substrates using experimental and computational methods.
520 $a The first part of the study comprises of an in vitro experimental investigation of the effect of fluid shear on the kinetics and receptor specificity of PMN-colon carcinoma cell adhesive interactions in cell suspensions using a rheometric-flow cytometric methodology. We demonstrate for the first time that L-selectin-mediated tethering is required for optimal PMN-colon carcinoma cell adhesion under high shear conditions (≥400 s -1). We also show that the L-selectin ligand on the metastatic LS174T cells is sialylated, O-linked and a protease-sensitive glycoprotein. In contrast, the non-metastatic HCT-8 cells, which do not possess the L-selectin ligand are unable to bind to PMNs under high shear conditions. Moreover, the contribution of PMN LFA-1 and Mac-1 to PMN-colon carcinoma cell stable adhesion is shown to be dependent on shear rate, shear exposure time and the ligands for the beta2 integrins.
520 $a In the second part of the study we used a computational model to simulate PSGL-1-mediated rolling of a deformable PMN on a P-selectin-coated surface under shear flow. We observed that the average rolling velocity of the cell and the cell-substrate contact area decrease with increasing membrane stiffness for shear rates ≥200 s-1. The lifetime of the P-selectin - PSGL-1 bond was found to decrease with increasing membrane stiffness at all shear rates examined.
520 $a Collectively, these findings may provide insights for the rational development of novel therapeutics to combat inflammation and cancer metastasis.
590 $a School code: 0098.
650 4 $a Engineering, Chemical. $3 1018531
650 4 $a Health Sciences, Oncology. $3 1018566
650 4 $a Health Sciences, Immunology. $3 1017716
650 4 $a Biophysics, Medical. $3 1017681
690 $a 0542
690 $a 0992
690 $a 0982
690 $a 0760
710 2 0 $a The Johns Hopkins University. $3 1017431
773 0 $t Dissertation Abstracts International $g 65-12B.
790 1 0 $a Konstantopoulos, Konstantinos, $e advisor
790 $a 0098
791 $a Ph.D.
792 $a 2005
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3155627