The Journal of the Japan Society for Respiratory Endoscopy

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CD13/aminopeptidase N (E.C.3.4.11.2) is an ectoenzyme located in the outer cell membrane in a variety of cells. Since CD13/aminopeptidase N was shown to induce in vitro chemotactic migration of human lymphocytes, we examined here the significance of CD13/aminopeptidase N in pulmonary sarcoidosis and radiation pneumonitis caused by a single-dose thoracic irradiation (15 Gy) in a rat model. The activity of aminopeptidase in bronchoalveolar lavage fluid (BALF) was significantly higher in sarcoidosis patients than in normal volunteers (NV) and control patients (CP). CD13/aminopeptidase N protein was detectable in alveolar macrophages (AN) from sarcoidosis patients at higher levels than in those from NV. Higher chemotactic activity for lymphocytes was detected in the BALF from sarcoidosis patients that in that from NV, and the activity was significantly decreased by the treatment with bestatin, an specific inhibitor for aminopeptidase N. Significantly increased CD13/aminopeptidase N activity and expression were also detected in BALF and AM obtained from irradiated rats at 4 weeks after irradiation compared with the activity in unirradiated rats. Chemotactic activity for normak rat lymphocytes was detected in BALF from irradiated rats at 4 weeks, and approximately 60% of the activity was inhibited by pretreatment of BALF with bestatin. This study suggests that CD13/aminopeptidase N may play an important role as a lymphocyte chemoattractant in lymphocyte-mediated alveolitis in interstitial lung diseases.

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Chemokines have been defined by their capacity to regulate traffic of immune cells. Here, we demonstrate that expression of β-chemokine RANTES in host cells (especially airway epithelial cells) infected with a respiratory virus enables immune cells to more efficiently migrate across the epithelial barrier. On this study, the patterns for specific apical sorting of RANTES may serve to mediate the level and directionality of immune cell traffic through epithelium (distinct from endothelium). This chemoattractant activities may efficiently regulate traffic of mucosal immune cell during normal host defense and abnormal inflammatory disease in the airway. Especially, RANTES has the pattern of preferential apical secretion provides for a soluble chemical gradient for immune cells movement from the subepithelium to the mucosal surface and maintenance there. In addition, we investigated RANTES deficiencies affect the delay on infiltrating cells movement on immunity response, and then the reduction of chemotactic activities (particular activated macrophages trafficking) were observed in airway epithelium level with viral infected RANTES deficient mice. The results therefore establish a distinct action of chemokines in regulating immune cell migration and the primary importance of this component of innate immunity for host defense.

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