Neutrophil Intercellular Communication in Acute Lung Injury. Emerging Roles of Microparticles and Gap Junctions

Abstract

A hallmark of acute inflammation involves the recruitment of polymorphonuclear leukocytes (neutrophils) to infected or injured tissues. The processes underlying this recruitment are complex, and include multiple mechanisms of intercellular communication between neutrophils and the inflamed tissue. In recent studies of the systemic and pulmonary vasculature, interest has increased in novel forms of intercellular communication, such as microparticle exchange and gap junctional intercellular communication. To understand the roles of these novel forms of communication in the onset, progression, and resolution of inflammatory lung injury (such as acute respiratory distress syndrome), we review the literature concerning the contributions of microparticle exchange and gap junctional intercellular communication to neutrophilalveolar crosstalk during pulmonary inflammation. By focusing on these cell-cell communications, we aim to demonstrate significant gaps of knowledge and identify areas of considerable need for further investigations of the processes of acute lung inflammation.Keywords: neutrophil; connexin; gap junction; microparticles; acute lung injury Although investigations of acute respiratory distress syndrome (ARDS) have yet to yield an efficacious pathophysiologytargeted therapy, they have provided important insights into the intercellular communications regulating neutrophil activation and alveolar transmigration. These communications include juxtacrine and paracrine (e.g., chemokines, cytokines, and proteinases), crosstalk between neutrophils and lung parenchymal cells, and the signaling conducted through cell-surface receptors such as leukocyte integrins and cognate adhesion molecules (e.g., intercellular adhesion molecules) expressed by lung parenchymal cells (1). The past decade has seen an increasing recognition of alternative forms of intercellular communications during the onset and resolution of inflammatory lung disease. These communications include microparticle exchange as well as gap junctional intercellular communication (GJIC). This Perspective will focus on these alternative forms of communication between neutrophils and lung parenchymal cells during the genesis of ARDS, highlighting opportunities for further investigations. MICROPARTICLE EXCHANGEMicroparticles are spherical, lipid bilayer-encapsulated extracellular bodies ranging from 50-1,000 nm in diameter. Microparticles can be secreted by almost every cell type, including lung parenchymal cells and inflammatory cells. Multiple forms of microparticles exist, reflecting different modes of production. "Exosomes" and "shedding vesicles" are derived from living cells, whereas "apoptotic bodies" are secreted by apoptotic and/or necrotic cells (2). Exosomes have an endosomal origin, and are stored as intraluminal vesicles within multivesicular bodies (3). Upon stimulation, exosomes are secreted by fusion with the cell membrane, forming a relatively homogenous group of microparticle sizes (50-150 nm). In contrast, shedding vesicles and apoptotic ...

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