ICAM-1 mediates leukocyte-endotheliumadhesive interactionsin the reversed passive Arthus reaction

A murine anti-rat intercellular adhesion molecule 1 (ICAM-!) monoclonal antibody (niAb), 1A29, was used to investigate the importance of blood leuko- cyte-associated 1�2-integrrn (CD 1 1/CD 1 8)/vascular endotheliuin.-.associated ICAM-! adhesive interactions in the reversed passive Arthus reaction (RPAR) in rats. An Arthus pleurisy reaction (4 h) was employed in these studies because it permits the accurate quantita- Lion of polymorphonuclear neutrophil (PMN) influx into the pleural space and fluid accumulation. 1A29, which localized within Arthus lung lesions, caused a dose-dependent (0.5-2.0 mgfkg, i.v.) inhibition of PMN influx (19-56%) and exudate volume (9-55%) in the Arthus pleurisy reaction. P7 (2 mgJkg, i.v.), a murine anti-human P-selectin mAb used as an iso- type-matched control lor 1A29, did not localize at the lung lesion site and was inactive. Immunohisto- chemical analysis of lung tissue from 1A29-treated rats demonstrated increased granulocyte accumula- tion in the alveolar capillaries compared with more extensive granulocyte emigration into the lung tissue and pleural space in P7-treated rats and Arthus con- trol rats; however, quantitative image analysis revealed increased numbers of lung granulocytes in 1A29- treated rats compared with controls. Neither ICAM- 1 mRNA nor expression, assessed by immunocyto- chemistry, was increased above control levels in rats during the pleural Arthus reaction. Neutropema was not observed in either 1A29- or P7-treated rats. J. Leukoc. Biol. 59: 333-340; 1996.