ICAM-1 MEDIATES LEUKOCYTE-ENDOTHELIUM ADHESIVE INTERACTIONS IN THE REVERSED PASSIVE ARTHUS REACTION

A murine anti-rat intercellular adhesion molecule 1 (ICAM-1)monoclonal antibody (mAb), 1A29, was used to investigate the importance of blood leukocyte-associated beta(2)-integrin (CD11/CD18)/vascular endotheliu m-associated ICAM-1 adhesive interactions in the reversed passive Arth us reaction (RPAR) in rats. An Arthus pleurisy reaction (4 h) was empl oyed in these studies because it permits the accurate quantitation of polymorphonuclear neutrophil (PMN) influx into the pleural space and f luid accumulation, 1A29, which localized within Arthus lung lesions, c aused a dose-dependent (0.5-2.0 mg/kg, i.v.) inhibition of PMN influx (19-56%) and exudate volume (9-55%) in the Arthus pleurisy reaction, P 7 (2 mg/kg, i.v.), a murine anti-human P-selectin mAb used as an isoty pe-matched control for 1A29, did not localize at the lung lesion site and was inactive, Immunohistochemical analysis of lung tissue from 1A2 9-treated rats demonstrated increased granulocyte accumulation in the alveolar capillaries compared with more extensive granulocyte emigrati on into the lung tissue and pleural space in P7-treated rats and Arthu s control rats; however, quantitative image analysis revealed increase d numbers of lung granulocytes in 1A29-treated rats compared with cont rols, Neither ICAM-1 mRNA nor expression, assessed by immunocytochemis try, was increased above control levels in rats during the pleural Art hus reaction, Neutropenia was not observed in either 1A29- or P7-treat ed rats.