title: Tumor necrosis factor alpha regulates in vivo intrapulmonary expression of ICAM-1.
abstract: Lung injury following deposition of IgG immune complexes is neutrophil-dependent and requires both tumor necrosis factor alpha (TNF alpha) and CD18. In the current studies, we have evaluated the relationship between TNF alpha and expression of intracellular adhesion molecule-1 (ICAM-1) in vitro and in vivo. In both rat pulmonary artery endothelial cells and human umbilical vein endothelial cells, TNF alpha induced an early (within 60 minutes) increase in ICAM-1 expression, followed by a peak at 6 to 8 hours, with relatively stable expression at 24 hours. Expression of E-selectin did not show the early phase (within 60 minutes) of up-regulation, peaked at 4 hours, and then declined thereafter. Using a radioimmunochemical assay in vivo, it was demonstrated that intrapulmonary deposition of IgG immune complexes caused a progressive increase in ICAM-1 expression in lung over an 8-hour period. In animals pretreated with antibody to TNF alpha, the intrapulmonary expression of ICAM-1 was significantly reduced. These results were confirmed by immunoperoxidase analysis of lung tissue. It was also shown that airway instillation of TNF alpha caused up-regulation of ICAM-1 in lung. These data support the concept that deposition of IgG immune complexes in lung induces intrapulmonary up-regulation of ICAM-1 in a manner that is TNF alpha-dependent.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
authors.forename: M S
authors.initials: MS
authors.lastname: Mulligan
authors.forename: A A
authors.initials: AA
authors.lastname: Vaporciyan
authors.forename: M
authors.initials: M
authors.lastname: Miyasaka
authors.forename: T
authors.initials: T
authors.lastname: Tamatani
authors.forename: P A
authors.initials: PA
authors.lastname: Ward
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D000936:Antigen-Antibody Complex / Q000378:metabolism; D015703:Antigens, CD / Q000502:physiology; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000378:metabolism; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1; D008168:Lung / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D011863:Radioimmunoassay; D051381:Rats; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000906:Antibodies; D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1