Cytokine-induced phagocyte adhesion to human mesangial cells: role of CD11/CD18 integrins and ICAM-1.
We examined the actions of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) on neutrophil and monocyte (phagocyte) adhesion to human mesangial cell monolayers (HMC) and assessed the role of phagocyte CD11/CD18 integrin adhesion molecules and HMC intercellular adhesion molecule-1 (ICAM-1) in this process, using subunit specific monoclonal antibodies (MAb). TNF, but not IL-1, provoked rapid (onset less than 1 min) neutrophil and monocyte adhesion to HMC by a phagocyte-directed action. Adhesion was markedly inhibited by MAb against CD18 and CD11b, with lesser or no inhibition being afforded by MAb against CD11a, CD11c, or ICAM-1. In contrast, prolonged exposure of HMC to TNF or IL-1 (1-18 h) increased HMC adhesiveness for phagocytes. These actions were blocked by actinomycin D or cycloheximide and by MAb against HMC ICAM-1 or phagocyte CD18, CD11a, or CD11b, suggesting that cytokines provoked adhesion by inducing HMC ICAM-1 synthesis. In keeping with this interpretation, TNF treatment of HMC was associated with increased ICAM-1 surface expression, as determined by indirect immunofluorescence, and increased ICAM-1 mRNA levels, as determined by Northern blot analysis. The actions of TNF on phagocytes and HMC were additive. HMC injury, as determined by 51Cr release, was only observed when both phagocytes and HMC were activated by TNF. HMC injury was attenuated by anti-CD18 MAb and superoxide dismutase, suggesting that the injury process was, in part, adhesion dependent and mediated by reactive oxygen species.(ABSTRACT TRUNCATED AT 250 WORDS)
Denton
M D
MD
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Marsden
P A
PA
Luscinskas
F W
FW
Brenner
B M
BM
Brady
H R
HR
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D018845:CD11 Antigens; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology*; D000939:Epitopes / Q000276:immunology; D005920:Glomerular Mesangium / Q000166:cytology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007375:Interleukin-1 / Q000494:pharmacology*; D009000:Monocytes / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D010586:Phagocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D000939:Epitopes; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1