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 endothelium-associated ICAM-1 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 quantitation 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 mg/kg, i.v.) inhibition of PMN influx (19-56%) and exudate volume (9-55%) in the Arthus pleurisy reaction. P7 (2 mg/kg, i.v.), a murine anti-human P-selectin mAb used as an isotype-matched control for 1A29, did not localize at the lung lesion site and was inactive. Immunohistochemical analysis of lung tissue from 1A29-treated rats demonstrated increased granulocyte accumulation in the alveolar capillaries compared with more extensive granulocyte emigration into the lung tissue and pleural space in P7-treated rats and Arthus control 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 immunocytochemistry, was increased above control levels in rats during the pleural Arthus reaction. Neutropenia was not observed in either 1A29- or P7-treated rats.
Smith
R J
RJ
Department of Cell Biology and Inflammation Research, Pharmacia and Upjohn, Inc., Kalamazoo, Michigan, USA.
Chosay
J G
JG
Dunn
C J
CJ
Manning
A M
AM
Justen
J M
JM
D000818:Animals; D000911:Antibodies, Monoclonal; D001183:Arthus Reaction / Q000276:immunology*; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology; D015870:Gene Expression; D006098:Granulocytes / Q000166:cytology* / Q000276:immunology; D007091:Image Processing, Computer-Assisted; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D008297:Male; D010996:Pleural Effusion / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1