Adhesion to extracellular matrix proteins modulates bovine neutrophil responses to inflammatory mediators

The neutrophil inflammatory response can be altered profoundly by contact with extracellular matrix proteins (ECMs). We characterized functional responses (intracellular calcium, actin polymerization, degranulation, adhesion, and oxidative burst) of bovine neutrophils adhered to selected ECM proteins [collagen IV, laminin, fibronectin, thrombospondin, and heparan sulfate proteoglycan (HSP)] in response to interleukin-8 (IL-8) and platelet-activating factor (PAF). Neutrophil adhesion to ECMs altered responses to PAF and IL-8, although some functions were more responsive to modulation. The most susceptible function was reactive oxygen species (ROS) production. ROS production in response to PMA and TNF-alpha was supported differentially by various ECMs, and PAF and IL-8 "priming" had strikingly different effects, depending on the ECM present. Although PAF and IL-8 inhibited TNF-alpha-induced ROS production in neutrophils adhered to collagen, fibronectin, and laminin, PAF enhanced ROS production strongly in HSP-adherent cells. This study illustrates how neutrophils can integrate multiple stimuli, resulting in complex modulation of their functional response.