IN-VIVO EXPRESSION OF INTERCELLULAR-ADHESION MOLECULE-1 IN TYPE-II PNEUMOCYTES DURING HYPEROXIA

Cell-to-cell communication is often disrupted when tissue damage occur s, triggering new signals to cope with the injury. The expression of i ntercellular adhesion molecule (ICAM-1), a protein involved in the mig ration, binding, and activation of leukocytes, is markedly increased i n mouse lungs damaged by acute hyperoxic exposure. Type I alveolar epi thelial cells are sensitive to hyperoxic lung injury, and must be remo ved from the air spaces following their destruction. In contrast, type II pneumocytes are relatively resistant to hyperoxia and may have a r ole in the removal process. Two reports demonstrate increased ICAM-1 i n alveoli after hyperoxia (Welty et al., 1993, AJRCMB 9:393-400; and K ang et al., 1993, AJRCMB 9:350-355), but the cellular site(s) of ICAM- 1 synthesis were not determined. We hypothesized that during in vivo e xposure to 100% oxygen (O-2), type II pneumocytes synthesize and secre te ICAM-1, an important step in attracting inflammatory cells to the s ite of injury. Adult mice were exposed to 100% O-2 for up to 72 h. To determine whether type II cells express ICAM-1, tissue sections were s tudied by electron microscopy single-label in situ hybridization or li ght microscopy dual-label in situ hybridization, using radiolabeled an d nonradiolabeled probes. In the lungs of unexposed animals, ICAM-1 mR NA was detected in many cells - including type I pneumocytes -but not in type II cells. After hyperoxia, ICAM-1 transcripts were detected in bonafide, surfactant protein C mRNA-containing, type II alveolar epit helial cells. This observation suggests that type II cells play an imp ortant and previously unrecognized role in pulmonary inflammation from O-2 toxicity and emphasizes the importance of type II pneumocytes in alveolar repair after injury.