title: Preferential binding of platelets to monocytes over neutrophils under flow.
abstract: This study was undertaken to systematically investigate the binding kinetics of platelet recruitment by monocytes relative to neutrophils in bulk suspensions subjected to shear as well as the molecular requirements of leukocyte-platelet binding. Hydrodynamic shear-induced collisions augment the proportion of monocytes with adherent platelets more drastically than that of neutrophils with bound platelets. These heterotypic interactions are further potentiated by platelet activation with thrombin or to a lesser extent by monocyte stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP). Monocyte-platelet heteroaggregation increases with increasing shear rate and shear exposure time. Platelet P-selectin binding to monocyte P-selectin-glycoprotein-ligand-1 is solely responsible for maximal platelet adhesion to unstimulated monocytes in shear flow. However, the enhanced platelet binding to fMLP-treated monocytes involves a sequential two-step process, wherein P-selectin-PSGL-1 interactions are stabilized by CD18-integrin involvement. Blocking platelet alpha(IIb)beta(3) or monocyte beta(1)-integrin function had no effect. This study underscores the preferential recruitment of platelets by monocytes relative to neutrophils in shear flow, and demonstrates that the shear environment of the vasculature coupled to the state of cell activation modulates the dynamics and molecular constituents mediating monocyte-platelet adhesion.
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Kyung C
authors.initials: KC
authors.lastname: Ahn
authors.forename: Andy J
authors.initials: AJ
authors.lastname: Jun
authors.forename: Parag
authors.initials: P
authors.lastname: Pawar
authors.forename: Sameer
authors.initials: S
authors.lastname: Jadhav
authors.forename: Susan
authors.initials: S
authors.lastname: Napier
authors.forename: Owen J T
authors.initials: OJ
authors.lastname: McCarty
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Konstantopoulos
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry; D001792:Blood Platelets / Q000166:cytology*; D018821:CD18 Antigens / Q000096:biosynthesis / Q000378:metabolism; D002412:Cations; D002448:Cell Adhesion; D002478:Cells, Cultured; D005434:Flow Cytometry; D006023:Glycoproteins / Q000737:chemistry; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D007700:Kinetics; D019041:L-Selectin / Q000096:biosynthesis / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D015233:Models, Statistical; D008962:Models, Theoretical; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000737:chemistry; D009504:Neutrophils / Q000166:cytology*; D019007:P-Selectin / Q000378:metabolism; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011485:Protein Binding; D013314:Stress, Mechanical; D013917:Thrombin / Q000378:metabolism; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D002412:Cations; D006023:Glycoproteins; D019012:Integrin beta1; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013917:Thrombin