Mediators and regulation of neutrophil accumulation in inflammatory responses in lung: insights from the IgG immune complex model.
Neutrophil trafficking in lung involves transendothelial migration, migration in tissue interstitium, and transepithelial migration. In a rat model of IgG immune complex-induced lung injury, it was demonstrated that neutrophil emigration involves regulatory mechanisms including complement activation, cytokine regulation, chemokine production, activation of adhesion molecules, and their respective counter receptors. The process is presumably initiated and modulated by the production of early response cytokines and chemokines from lung cells, especially from alveolar macrophages. TNF-alpha and IL-1 up-regulate intracellular adhesion molecule-1 (ICAM-1) and E-selectin, setting the stage for neutrophil migration through endothelium. The CXC chemokines, such as macrophage inflammatory protein (MIP)-2 and cytokine-inducible neutrophil chemoattractant (CINC), constitute chemokine gradient to orchestrate neutrophil migration in lung. Complement activation induced by IgG immune complex deposition is another important event leading to neutrophil accumulation in lung. Complement activation product C5a not only plays an important role in chemoattracting neutrophils into lung, but regulates adhesion molecules, chemokines, and cytokines expression. In addition, oxidative stress may regulate neutrophil accumulation in lung by modulation of adhesion molecule activation and chemokine production. In this review, we focus on the current knowledge of the mechanisms leading to accumulation of neutrophils during acute lung injury.
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
Ren-Feng
RF
Guo
Peter A
PA
Ward
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D018375:Neutrophil Activation / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D011014:Pneumonia / Q000276:immunology*; D051381:Rats
D000936:Antigen-Antibody Complex; D016207:Cytokines; D007074:Immunoglobulin G