No abstract

Acid-aspiration-induced injury is one of the leading causes of adult respiratory distress syndrome. Intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte-function-associated antigen-1 alpha (LFA-1 alpha), and it has been shown to be required for leukocyte migration into inflamed areas. The purpose of this report was to investigate the role of the ICAM-1/LFA-1 alpha pathway in a rat model of acid-aspiration-induced injury. Animals received 3.0 ml/kg HCI (0.1N; pH, 1.0) intratracheally pretreated with control monoclonal antibodies (mAbs) (HCI group) or anti-ICAM-1 and LFA-1 alpha mAbs (Test group). In the HCI group, increases in lung resistance (RL) (229 +/- 23% baseline), lung wet-to-dry weight ratio (W/D) (11.9 +/- 0.4), protein concentration (TP) (0.447 +/- 0.054 mg/ml), and the number of neutrophils (PMN) (159.0 +/- 19.4 x 10(4)) of bronchoalveolar lavage fluid were observed. In the Test group, HCI-induced injury was significantly reduced (RL, 122 +/- 7% baseline; W/D, 7.2 +/- 0.1; TP, 0.277 +/- 0.016 mg/ml; PMN, 8.8 +/- 0.8 x 10(4)). The administration of mAbs to ICAM-1 and LFA-1 alpha after HCI instillation partially attenuated HCI-induced responses. These observations suggest that the ICAM-1/LFA-1 alpha pathway might be involved in the pathogenesis of adult respiratory distress syndrome caused by acid aspiration.

We investigated the effects of tobacco smoke exposure on the production of tumor necrosis factor α (TNFα) by alveolar macrophages (AM) in mice (C57BL/6). The results obtained are as follows: (1) In vivo tobacco smoke exposure caused a significant decrease in the production of TNFα by AM with the stimulation of lipopolysaccharide (LPS; control group: 19.32 ± 5.52 U/ml, smoked group: 4.28 ± 0.98 U/ml; p < 0.05). (2) In vitro exposure of AM to tobacco smoke extracts (water-soluble extracts) also caused a decrease in the production of TNFα up to 93% of control with stimulation of LPS (p < 0.05) without any decrease in cellular viability. We concluded that the production of TNFα by AM was impaired by smoking via direct action of the factors present in tobacco smoke.

No abstract

Bleomycin-induced lung injury has been extensively used as a model of interstitial pneumonia and pulmonary fibrosis. Intercellular adhesion molecule (ICAM)-1 is a ligand for lymphocyte function-associated antigen (LFA)-1alpha and has been shown to be required for leukocyte migration into inflamed areas. The purpose of this report was to investigate the role of the ICAM-1/LFA-1alpha pathway in a murine model of bleomycin-induced lung injury. Animals received 75 mg x kg(-1) bleomycin (BLM) i.v. followed by treatment with phosphate-buffered saline (BLM group), anti-ICAM-1 and LFA-1alpha monoclonal antibodies (mAb) (BLM+mAb group). Inflammatory cell counts of bronchoalveolar lavage (BAL) fluid, hydroxyproline content and histological findings were compared between these groups. In the BLM group, significant increases in total cell count, macrophage count and neutrophil count of BAL fluid were observed on days 7 and 14. In the BLM+mAb group, bleomycin-induced accumulation of neutrophils was significantly reduced on days 7 and 14 (p<0.01). However, the administration of mAb to ICAM-1 and LFA-1alpha did not decrease the lung hydroxyproline content or the histopathological fibrosis grading score, indicating that the antagonism of ICAM-I and LFA-1alpha did not attenuate bleomycin-induced pulmonary fibrosis. This study suggests that the intercellular adhesion molecule-1/lymphocyte function-associated antigen-1alpha pathway mediates the accumulation of inflammatory cells in the injured lung caused by bleomycin; however, other mechanisms are important for the subsequent development of pulmonary fibrosis.