Effects of plasma, tumour necrosis factor, endotoxin and dexamethasone on extracellular proteolysis by neutrophils from healthy subjects and patients with emphysema.
1. Neutrophils from patients with chronic obstructive bronchitis and emphysema or age-matched control subjects were cultured on a substrate of 125I-fibronectin. The neutrophils from patients with lung disease digested significantly more fibronectin and released more elastase into the culture supernatant than did cells from control subjects. Preincubation of neutrophils from emphysematous patients with plasma from control subjects significantly inhibited fibronectin digestion by the patients' neutrophils by, on average, 10%. Preincubation of control subjects' neutrophils with plasma from emphysematous patients had no effect on fibronectin digestion. 2. Tumour necrosis factor increased fibronectin digestion in a dose-dependent manner when the cytokine was added to the adherent cells but not when preincubated with the polymorphonuclear leucocytes in suspension. Bacterial endotoxin in concentrations above 6 micrograms/ml significantly increased fibronectin digestion by neutrophils, but leukotriene B4, interferon-gamma and interleukin-1 alpha had no significant effects. 3. Dexamethasone inhibited fibronectin digestion by neutrophils in a dose-dependent manner, from 11% at 10(-10) mol/l to 68% at 10(-3) mol/l.
Lung Immunobiochemical Research Laboratory, The General Hospital, Birmingham, U.K.
D
D
Burnett
A
A
Chamba
S L
SL
Hill
R A
RA
Stockley
D000368:Aged; D001991:Bronchitis / Q000097:blood*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D005110:Extracellular Space; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010949:Plasma; D011656:Pulmonary Emphysema / Q000097:blood*; D014118:Toxins, Biological / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004731:Endotoxins; D005353:Fibronectins; D014118:Toxins, Biological; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone