L-selectin shear thresholding modulates leukocyte secondary capture.
Transient homotypic adhesions between flowing leukocytes and those previously adherent on the vessel wall has been proposed to amplify the accumulation of leukocytes at sites of inflammation. While adhesion of leukocytes to the vessel wall (primary capture) is mediated primarily by P-selectin on the endothelium and P-selectin Glycoprotein Ligand-1 (PSGL-1) on the leukocyte, the homotypic interactions leading to downstream leukocyte adhesion (secondary capture) are mediated primarily by reciprocal interactions between PSGL-1 and L-selectin on apposing leukocytes. One consequence of leukocyte secondary capture events are the formation of strings of adherent leukocytes as each recently captured leukocyte in turn captures another one flowing over its surface. Interestingly, PSGL-1-L-selectin interactions also mediate leukocyte hydrodynamic shear thresholding, whereby leukocyte rolling on purified L-selectin ligands such as PSGL-1 is maximized at a wall shear stress of approximately 1 dyne/cm(2) and minimized at both higher and lower flow rates. Using a novel quantitative method, we analyzed leukocyte string formation in vitro and found that hydrodynamic shear thresholding precluded secondary capture at low shear stresses yet amplified it at high shear stresses. Addition of the L-selectin mAb DREG-56 strongly inhibited leukocyte string formation, suggesting adhesion contributed significantly to hydrodynamic interactions in secondary capture processes. Taken together, the data suggest that secondary capture is modulated by the shear thresholding property of L-selectin. L-selectin mediated shear thresholding may therefore play a significant role in the regulation of leukocyte secondary capture in addition to recently described hydrodynamic recruitment mechanisms.
Paschall
Christopher D
CD
Department of Biomedical Engineering, University of Virginia, 415 Lane Road, Charlottesville, VA 22908, USA.
Lawrence
Michael B
MB
D000222:Adaptation, Physiological / Q000502:physiology; D001783:Blood Flow Velocity / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D004056:Differential Threshold / Q000502:physiology; D006801:Humans; D019041:L-Selectin / Q000502:physiology*; D007962:Leukocytes / Q000166:cytology* / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D008955:Models, Cardiovascular; D033081:Shear Strength; D013314:Stress, Mechanical
D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D019041:L-Selectin