MICE DEFICIENT IN ICAM-1 EXPRESSION AND WITH REDUCED CD18 EXPRESSION HAVE INCREASES IN HYPEROXIC LUNG INFLAMMATION AND INJURY. • 2337

Abstract

Treatment with supplemental oxygen is frequently used in premature infants because of abnormal lung function. While frequently essential to sustain life, the treatment may cause lung injury. Recently, there has been renewed interest in lung inflammation in hyperoxic lung injury. Investigators have determined that inhibition of the adhesion molecules, intercellular adhesion molecule-1(ICAM-1), and neutrophil (PMN) β2 integrins with monoclonal antibodies (mab) inhibits lung inflammation and injury in hyperoxic mice. However, mab administration may not be entirely specific so that mabs may have effects other than inhibiting adhesion molecules. We therefore placed mice with absent ICAM-1 expression, and mice with reduced β2-integrin expression in >95% oxygen and measured lung inflammation and injury as a function of hyperoxia-exposure time. In all studies wild-type mice on the same genetic background were used as controls. In the two mutant strains of mice there were increases in lung PMN counts when compared to the wild-type controls. In addition, lung weights were significantly greater in ICAM-1 deficient mice than in C57/BL6 at 72 h of hyperoxia-exposure. When mice were exposed to hyperoxia for 84 hours there were 12/12, 3/6 and 0/6 survivors in C57/BL6, ICAM-1 and β2 integrin mice respectively (P<0.05). In conclusion, mice with defects in ICAM-1 and β2-integrin expression are more susceptible to hyperoxic lung injury and have increased lung inflammation than their wild type counterparts. The apparent contradiction in our results with the mab studies suggests that the role of lung neutrophil accumulation in hyperoxic lung injury is more complex than previously appreciated, and that PMN accumulation occurring late in the course of hyperoxia-exposure is ICAM-1/β2 integrin independent.Table