title: αVβ3Integrin Regulation of Respiratory Burst in Fibrinogen Adherent Human Neutrophils.
abstract: In response to inflammatory stimuli, microvascular endothelial cells become activated, initiating the capture and exit of neutrophils from the blood vessel and into the extravascular extracellular matrix (ECM). In the extravascular space, neutrophils bind to ECM proteins, regulating cellular functions via signaling through adhesion molecules known as integrins. The αVβ3integrin is an important mediator of neutrophil adhesion to ECM proteins containing the Arg-Gly-Asp (RGD) peptide sequence, including fibrinogen and fibronectin. Despite the abundance of RGD sequence in the ECM, adhesion molecule-mediated neutrophil activity has been focused on the β2(Mac-1, CD11b/CD18) and β1integrin response to matrix proteins. Here we investigated αVβ3integrin-mediated reactive oxidant suppression as a consequence of human neutrophil adhesion to RGD containing proteins. Using integrin ligand-modified (poly)ethylene glycol hydrogels and reactive oxygen species (ROS) sensitive fluorescent probes (dihydrotetramethylrhosamine, H2TMRos), we evaluated integrin-peptide interactions that effectively regulate ROS generation. This study demonstrates that neutrophil adhesion suppresses ROS production in an αVβ3-dependent manner. Additionally, we determine that p38 mitogen-activated protein kinase in the respiratory burst signaling pathway is interrupted by integrin-mediated adhesion. These data indicate that ECM/integrin interactions can induce αVβ3-mediated adhesion dependent downstream signaling of ROS regulation via a Mac-1 independent mechanism.
authors: Department of Biomedical Engineering, Malone Engineering Center 314, Yale University, 55 Prospect Street, New Haven, CT 06511, USA.
authors: Hye-Yeong
authors: HY
authors: Kim
authors: Department of Biomedical Engineering, Malone Engineering Center 314, Yale University, 55 Prospect Street, New Haven, CT 06511, USA.
authors: Eleni A
authors: EA
authors: Skokos
authors: Department of Biomedical Engineering, Malone Engineering Center 314, Yale University, 55 Prospect Street, New Haven, CT 06511, USA.
authors: Deborah J
authors: DJ
authors: Myer
authors: Department of Biomedical Engineering, Malone Engineering Center 314, Yale University, 55 Prospect Street, New Haven, CT 06511, USA.
authors: Perez
authors: P
authors: Agaba
authors: Department of Biomedical Engineering, Malone Engineering Center 314, Yale University, 55 Prospect Street, New Haven, CT 06511, USA.
authors: Anjelica L
authors: AL
authors: Gonzalez
keywords: Adhesion; Extracellular matrix (ECM); Polyethylene glycol (PEG); Reactive oxygen species (ROS)
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