Activity of pulmonary edema fluid interleukin-8 bound to α₂-macroglobulin in patients with acute lung injury

Abstract

The formation of alpha(2)-macroglobulin (alpha(2)-M)/interleukin-8 (IL-8) complexes may influence the biological activity of IL-8 and the quantitative assessment of IL-8 activity. Therefore, in this study, concentrations of free IL-8 and IL-8 complexes with alpha(2)-M were measured in pulmonary edema fluid samples from patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and compared with control patients with hydrostatic pulmonary edema. Patients with ALI/ARDS had significantly higher concentrations of alpha(2)-M (P < 0.01) as well as alpha(2)-M/IL-8 complexes (P < 0.05). Because a substantial amount of IL-8 is complexed to alpha(2)-M, standard assays of free IL-8 may significantly underestimate the concentration of biologically active IL-8 in the distal air spaces of patients with ALI/ARDS. Furthermore, IL-8 bound to alpha(2)-M retained its biological activity, and this fraction of IL-8 was protected from proteolytic degradation. Thus complex formation may modulate the acute inflammatory process in the lung.

The mercurial nature of neutrophils: still an enigma in ARDS?

“…Although the related CXC chemokines CXCL5 (ENA-78) and CXCL1 (Gro-␣) are also elevated in BALF from ARDS patients (63), only IL-8 consistently correlates with the number of neutrophils and disease severity (61,176). Furthermore, IL-8 has been demonstrated to be the most potent neutrophil chemoattractant in BALF from ARDS patients and was the predominant neutrophilic chemokine released from LPS-stimulated human alveolar macrophages (62,101,127). Therefore IL-8 is considered the main neutrophil chemoattractant in ARDS.…”

Novel aspects of urokinase function in the injured lung: role of α2-macroglobulin

“…Lung fluids from patients with ALI/ARDS contain significantly elevated concentrations of ␣ 2 -M, due primarily to increased pulmonary alveolar-capillary membrane permeability. On the other hand, this protein is practically undetectable in normal lung lavage fluid (15,23,43).…”

“…Moreover, increased production of PAI-1 in patients with ALI/ARDS is partially responsible for the decrease in amount of active uPA and promotes fibrin deposition within the alveolar spaces of patients with ALI/ARDS (11,16,17,38). Since our previous studies indicate that ␣ 2 -M present in lung edema fluids from patients with ALI/ARDS retains its antiproteolytic activity, and ␣ 2 -M has been suggested to act as an uPA inhibitor, we tested the hypothesis that ␣ 2 -M affects function of uPA in the injured human lung (23,31).…”

“…Lung fluids from patients with ALI/ARDS contain significantly elevated concentrations of ␣ 2 -M, due primarily to increased pulmonary alveolar-capillary membrane permeability. On the other hand, this protein is practically undetectable in normal lung lavage fluid (15,23,43).Urokinase (uPA), a serine protease, catalyzes the activation of plasminogen to plasmin and is regulated by plasminogen activator inhibitor type 1 (PAI-1). Moreover, increased production of PAI-1 in patients with ALI/ARDS is partially responsible for the decrease in amount of active uPA and promotes fibrin deposition within the alveolar spaces of patients with ALI/ARDS (11,16,17,38).…”

Leukotriene B4 indicates lung injury and on-going inflammatory changes after severe trauma in a porcine long-term model

“…interleukin (IL)−8 into the pulmonary interstitium, release proteolytic enzymes and induce microvascular damage and harmful airway remodeling in lung tissue, which is associated with poor survival [9][10][11][12]. Moreover, the generation of inflammatory mediators including interleukin IL-8 plays an important role in ARDS pathophysiology [13][14][15][16].…”