Am. J. Respir. Crit. Care Med., Volume 161, Number 5, May 2000, 1689-1697

Inhibition of Binding of E- and P-selectin to Sialyl-Lewis X Molecule Suppresses the Inflammatory Response in Hypersensitivity Pneumonitis in Mice

LI-HUA PAN, KOHEI YAMAUCHI, TAKASHI SAWAI, TOSHIHIDE NAKADATE, YUKI KOJIMA, NAOFUMI TAKAHASHI, KEISUKE ADACHI, AKIHIKO KAMEYAMA, and HIROSHI INOUE

Third Department of Internal Medicine and First Department of Pathology, Iwate Medical University, School of Medicine, Morioka; and Pharmaceutical Division, Nisshin Oil Mills, Ltd., Yokohama, Japan

The carbohydrate structure of sialyl-Lewis X (SLe^x) can function as a ligand for E- and P-selectin, which play important roles in mediating the initial interactions of leukocytes with the endothelium in inflammatory responses. In this study we evaluated the effects of inhibiting E- and P-selectin function with the SLe^x molecule on the inflammatory response in an experimental murine model of hypersensitivity pneumonitis (HP). Antigen exposure induced marked interstitial and especially perivascular and peribronchiolar infiltration with lymphocytes and granuloma formation, in murine lung sensitized with Saccaropolyspora rectivirgula. These pathologic changes were significantly suppressed with SLe^x ganglioside analogues through a reduction in the numbers of lymphocytes in bronchoalveolar lavage fluid, as evidenced by the lung index and histologic scores indicating the severity of the inflammatory response. Using specific antibodies, we also evaluated the immunohistochemical localization of SLe^x in mononuclear cells in granulomas, and of E- and P-selectin in vascular endothelium. Our findings suggest that the molecular interaction between SLe^x, and E- and P-selectin mediates lymphocyte recruitment into the lung parenchyma, which is critical for the inflammatory response in experimental murine models of HP.

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