Fluid shear stress increases neutrophil activation via platelet-activating factor.
Leukocyte exposure to hemodynamic shear forces is critical for physiological functions including initial adhesion to the endothelium, the formation of pseudopods, and migration into tissues. G-protein coupled receptors on neutrophils, which bind to chemoattractants and play a role in neutrophil chemotaxis, have been implicated as fluid shear stress sensors that control neutrophil activation. Recently, exposure to physiological fluid shear stresses observed in the microvasculature was shown to reduce neutrophil activation in the presence of the chemoattractant formyl-methionyl-leucyl-phenylalanine. Here, however, human neutrophil preexposure to uniform shear stress (0.1-2.75 dyn/cm(2)) in a cone-and-plate viscometer for 1-120 min was shown to increase, rather than decrease, neutrophil activation in the presence of platelet activating factor (PAF). Fluid shear stress exposure increased PAF-induced neutrophil activation in terms of L-selectin shedding, αMβ2 integrin activation, and morphological changes. Neutrophil activation via PAF was found to correlate with fluid shear stress exposure, as neutrophil activation increased in a shear stress magnitude- and time-dependent manner. These results indicate that fluid shear stress exposure increases neutrophil activation by PAF, and, taken together with previous observations, differentially controls how neutrophils respond to chemoattractants.
Department of Biomedical Engineering, Cornell University, Ithaca, New York.
Michael J
MJ
Mitchell
Department of Biomedical Engineering, Cornell University, Ithaca, New York.
Kimberly S
KS
Lin
Department of Biomedical Engineering, Cornell University, Ithaca, New York. Electronic address: mike.king@cornell.edu.
Michael R
MR
King
D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D006439:Hemodynamics; D006801:Humans; D019041:L-Selectin / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D051379:Mice; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology*; D033081:Shear Strength; D013314:Stress, Mechanical; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016177:Macrophage-1 Antigen; D010972:Platelet Activating Factor; D019041:L-Selectin; D048051:p38 Mitogen-Activated Protein Kinases; D051722:ADAM Proteins; D000072198:ADAM17 Protein