Proinflammatory activity of anti-IL-8 autoantibody:IL-8 complexes in alveolar edema fluid from patients with acute lung injury.
A significant fraction of IL-8 in lung fluids from patients with the acute lung injury (ALI) is associated with anti-IL-8 autoantibodies (anti-IL-8:IL-8 complexes), and lung fluid concentrations of these complexes correlate with development and outcome of ALI. In this study, we examined whether anti-IL-8:IL-8 complexes exhibit proinflammatory activity in vitro. These complexes were purified from pulmonary edema fluid samples obtained from patients with ALI. First, we found that IL-8 bound to the autoantibody retained its ability to trigger chemotaxis of neutrophils, whereas control antibody did not have significant chemotactic activity. Next, we examined the ability of anti-IL-8:IL-8 complexes to induce neutrophil activation, i.e., neutrophil respiratory burst and degranulation. Anti-IL-8:IL-8 complexes triggered superoxide and myeloperoxidase release from human neutrophils, and in contrast, the control antibody had no effect. We also demonstrated that IgG receptor, FcgammaRIIa, is the receptor involved in cellular activation mediated by these complexes. Blockade of FcgammaRIIa completely reverses activity of the complexes with the exception of chemotaxis. Both FcgammaRIIa and IL-8 receptors mediate chemotactic activity of anti-IL-8:IL-8 complexes, with FcgammaRIIa being, however, a predominant receptor. Furthermore, activity of the complexes is partially dependent on the activation of the mitogen-activated protein kinases, i.e., ERK and p38, important components of the FcgammaRIIa signaling cascade. Anti-IL-8:IL-8 complexes may therefore be involved in the pathogenesis of lung inflammation in clinical acute lung injury.
Krupa
Agnieszka
A
Department of Biochemistry, University of Texas Health Center, 11937 US Highway 271, Tyler, TX 75708-3154, USA.
Kato
Hiroyuki
H
Matthay
Michael A
MA
Kurdowska
Anna K
AK
D000936:Antigen-Antibody Complex / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology*; D015153:Blotting, Western; D002633:Chemotaxis / Q000276:immunology; D015633:Extravascular Lung Water / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000276:immunology*; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000276:immunology; D011654:Pulmonary Edema / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D001323:Autoantibodies; C080568:Fc gamma receptor IIA; D016209:Interleukin-8; D017452:Receptors, IgG