Up-regulation of lung vascular ICAM-1 in rats is complement dependent.
Intrapulmonary deposition of IgG immune complexes in rats causes acute inflammatory lung injury that is neutrophil, complement, cytokines (IL-1, TNF-alpha), and intercellular adhesion molecule (ICAM-1) dependent. In the current studies involving the same model of lung injury, complement depletion or complement blockade resulted in substantial reductions in up-regulation of pulmonary vascular ICAM-1, accompanied by reduced lung injury and neutrophil accumulation. Complement depletion neither reduced the amount of immune complex deposited in lung nor the TNF-alpha content in bronchoalveolar lavage fluids. In the same model of inflammatory lung injury, neutrophil depletion (which is highly protective) did not affect up-regulation of lung vascular ICAM-1. Up-regulation of lung vascular ICAM-1 by intratracheally administered TNF-alpha was also prevented by complement depletion. These studies indicate an unexpected in vivo relationship between complement and up-regulation of lung vascular ICAM-1.
Vaporciyan
A A
AA
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.
Mulligan
M S
MS
Warren
J S
JS
Barton
P A
PA
Miyasaka
M
M
Ward
P A
PA
D000818:Animals; D000936:Antigen-Antibody Complex / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid; D003165:Complement System Proteins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D007322:Instillation, Drug; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000098:blood supply*; D008297:Male; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*
D000936:Antigen-Antibody Complex; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D003165:Complement System Proteins; D009195:Peroxidase