Molecular Mechanisms of Neutrophil-Mediated Pulmonary Microvascular Injury: Role of Adhesion Proteins

Abstract

Neutrophils are important effector cells in the pathogenesis of acute lung injury. Recent studies indicate that the primary interaction between the neutrophil and the endothelial cell barrier is mediated by the cell surface neutrophil adhesive glycoprotein complex CD11/CD18 (Wright 1981). The understanding of this mechanism of interaction between the neutrophil and endothelial cells is needed to better describe the basis of neutrophil-mediated lung vascular injury (Fig. 1). The neutrophil CD18 adhesion glycoprotein complex interacts with endothelial cell surface ligand intercellular adhesion molecule-1 (ICAM-1), which is present constitutively and which can be up-regulated in response to cytokines (Fig. 1) (Pober 1986). Another important aspect of this interaction is that neutrophil attachment to the endothelial cell enhances the neutrophil activation responses such as the generation of oxidants and proteases (Fig. 1) (Nathan 1987). The release of neutrophil-derived products at sites of attachment of neutrophils to endothelial cells mediate endothelial injury and increase endothelial permeability.