found that OPN bound to histones with high affinity in vitro (Kd=2.8×10-7 for histone H3.1 and Kd=1.4×10-8 for histone H4 determined by surface plasmon resonance) and that the histone–OPN complex levels in the bronchoalveolar lavage fluid of ARDS patients were significantly higher than those in the bronchoalveolar lavage fluid of healthy individuals (144). Here, SPP1 is linked to acute respiratory distress syndrome.