Anti-Chemokine Autoantibody:Chemokine Immune Complexes Activate Endothelial Cells via IgG Receptors

Krupa, Agnieszka; Fudala, Rafał; Stankowska, Dorota; Loyd, Tameka; Allen, Timothy Craig; Matthay, Michael A.; Gryczyński, Zygmunt; Gryczyński, Ignacy; Mettikolla, Yalla V.; Kurdowska, Anna

doi:10.1165/rcmb.2008-0183oc

Cited by 15 publications

(32 citation statements)

References 39 publications

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“…Further, when we examined lung tissue from patients with lung injury for anti-IL-8 autoantibody: IL-8 immune complexes, we found these complexes in the lungs of patients with ARDS, in association with FcgRIIa (10). Our previous findings also indicate that the expression of FcgRIIa is substantially increased in the lungs of patients with ARDS (9,10).…”

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confidence: 58%

“…Previous observations by our laboratory indicate that the presence of anti-IL-8 autoantibody:IL-8 immune complexes (IL-8 associated with anti-IL-8 autoantibodies) in lung fluid from patients with ALI/ARDS comprises an important prognostic indicator of the development and ultimate outcome of ALI/ARDS (4-6). In addition, our studies were the first to show that purified anti-IL-8 autoantibody:IL-8 immune complexes display proinflammatory activity toward neutrophils and endothelial cells through the engagement of FcgRIIa (7)(8)(9). Further, when we examined lung tissue from patients with lung injury for anti-IL-8 autoantibody: IL-8 immune complexes, we found these complexes in the lungs of patients with ARDS, in association with FcgRIIa (10).…”

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confidence: 89%

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Bruton’s Tyrosine Kinase Mediates FcγRIIa/Toll-Like Receptor–4 Receptor Crosstalk in Human Neutrophils

Krupa

Fudala

Florence³

et al. 2013

Am J Respir Cell Mol Biol

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Previous observations by our laboratory indicate that the presence of anti-IL-8 autoantibody:IL-8 immune complexes in lung fluids from patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) comprises an important prognostic indicator in the development and ultimate outcome of ALI/ARDS. We also showed that these complexes display proinflammatory activity toward neutrophils through the engagement of FcgRIIa receptors. Because sepsis is one of the most common risk factors for ALI/ARDS, the initial goal of our present study involved investigating the effects of LPS on the expression of FcgRIIa receptors in neutrophils. Our results indicate that LPS triggers an increase in the expression of FcgRIIa on the neutrophil surface, which leads to shortening of the molecular distance between FcgRIIa and Toll-like receptor-4 (TLR4). When such neutrophils are stimulated with anti-IL-8:IL-8 complexes, the TLR4 cascade becomes activated via the engagement of FcgRIIa. The underlying molecular mechanism has been subsequently examined and involves Bruton's tyrosine kinase (Btk). In conclusion, our study reveals the existence of Btk-dependent molecular cooperation between FcgRIIa and TLR4 signaling cascades in LPS-"primed" human neutrophils. Furthermore, we used fluorescence lifetime imaging to study the interactions between TLR4 and FcgRIIa in human alveolar neutrophils from patients with ALI/ARDS. The results from these experiments confirm the existence of the molecular cooperation between TLR4 and FcgRIIa.Keywords: neutrophil; FcуRIIa; TLR4; Btk Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is characterized by diffuse, acute lung injury with a significant increase in both the total number of neutrophils and the proportion of neutrophils within alveolar spaces (1). Although neutrophils constitute only 0.8-3% of nonstructural alveolar cells in normal subjects, they account for 70-80% of the cells in bronchoalveolar (BAL) fluid from patients with ARDS (2, 3). Previous observations by our laboratory indicate that the presence of anti-IL-8 autoantibody:IL-8 immune complexes (IL-8 associated with anti-IL-8 autoantibodies) in lung fluid from patients with ALI/ARDS comprises an important prognostic indicator of the development and ultimate outcome of ALI/ARDS (4-6). In addition, our studies were the first to show that purified anti-IL-8 autoantibody:IL-8 immune complexes display proinflammatory activity toward neutrophils and endothelial cells through the engagement of FcgRIIa (7-9). Further, when we examined lung tissue from patients with lung injury for anti-IL-8 autoantibody: IL-8 immune complexes, we found these complexes in the lungs of patients with ARDS, in association with FcgRIIa (10). Our previous findings also indicate that the expression of FcgRIIa is substantially increased in the lungs of patients with ARDS (9, 10).Sepsis is a major risk factor for the development of ALI/ARDS, and LPS is a likely cause of progression to ALI/ARDS (1). Tolllike receptor-4 (TLR4), a receptor for LPS, ...

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confidence: 58%

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confidence: 89%

Bruton’s Tyrosine Kinase Mediates FcγRIIa/Toll-Like Receptor–4 Receptor Crosstalk in Human Neutrophils

Krupa

Fudala

Florence³

et al. 2013

Am J Respir Cell Mol Biol

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“…These complexes have also recently been shown to trigger an inflammatory phenotype in endothelial cells, including activation of both the MAPK and NF-κB signaling cascade and upregulation of ICAM-1 (121). This effect is mediated by engagement of anti-IL-8 autoantibody:IL-8 complexes with the IgG receptor FcgRIIa on the surface of endothelium (120). Collectively, these observations illustrate the ability of autoantibodies to amplify chemokine-dependent inflammatory lung injury.…”

Section: Immunomodulators Of Chemokine Bioactivitymentioning

confidence: 79%

Growth Factors and Cytokines in Acute Lung Injury

Deng

Standiford

2010

Comprehensive Physiology

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Cytokines and growth factors play an integral role in the maintenance of immune homeostasis, the generation of protective immunity, and lung reparative processes. However, the dysregulated expression of cytokines and growth factors in response to infectious or noxious insults can initiate and perpetuate deleterious lung inflammation and fibroproliferation. In this article, we will comprehensively review the contribution of individual cytokines and growth factors and cytokine networks to key pathophysiological events in human and experimental acute lung injury (ALI), including inflammatory cell recruitment and activation, alveolar epithelial injury and repair, angiogenesis, and matrix deposition and remodeling. The application of cytokines/growth factors as prognostic indicators and therapeutic targets in human ALI is explored.

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“…Indeed, it is well established that apoptosis of neutrophils is delayed in patients with ARDS (103). In addition, these IL-8 immune complexes activate endothelial cells, which upregulate ICAM-1 and increase ERK, JNK, and Akt phosphorylation (95), which may suggest that IL-8 immune complexes can induce endothelial cells to release proinflammatory mediators. Indeed, Fc␥RIIa is expressed on several cell types in the ARDS lung, including endothelial cells, neutrophils, and cells of the myeloid lineage, such as macrophages, monocytes, and dendritic cells (4).…”

Section: Il-8 Immune Complexes In Ardsmentioning

confidence: 99%