Triggering of respiratory burst by tumor necrosis factor in neutrophils adherent to fibronectin. Evidence for a crucial role of CD18 glycoproteins.
Human neutrophils, plated on fibronectin (FN)-coated wells, were found to release large quantities of superoxide anion (O2-) in response to tumor necrosis factor alpha (TNF-alpha). The O2- release was completely inhibited by two monoclonal antibodies (MoAbs, MHM23 and TS1/18) against CD18 glycoproteins. An independently derived anti-CD18 MoAb (60.3) was ineffective. These MoAbs failed to inhibit neutrophil adhesion to FN-coated surfaces. Moreover, neutrophils incubated for 30 min on FN and then washed to remove non-adherent cells, were responsive to TNF-alpha in the presence of anti-CD18 MoAbs MHM23 and TS1/18. Consequently, the CD18-dependent capacitation of the respiratory burst can occur before TNF-alpha triggering. Finally, neutrophils plated on FN in the presence of anti-CD18 MoAbs and then washed, i.e. adherent cells blocked in their surface CD18 molecules, released O2- after adding TNF-alpha but only in the absence of additional anti-CD18 MoAbs. This is consistent with a TNF-alpha ability to induce rapid expression and activation of new oxidative burst-capacitating CD18 molecules. The results suggest that the anchorage of neutrophils to FN surfaces depends on adherence molecules apparently unrelated to CD18, probably the so-called fibronectin receptors (FNRs), whereas the capacitation of the respiratory burst in response to TNF-alpha requires the intervention of CD18 glycoproteins, available on the membrane of "resting" neutrophils or mobilized to the cell surface by TNF-alpha.
Ottonello
L
L
Department of Internal Medicine, University of Genova Medical School, Italy.
Dapino
P
P
Scirocco
M
M
Barbera
P
P
Dallegri
F
F
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D018821:CD18 Antigens; D002448:Cell Adhesion; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology / Q000502:physiology*; D016897:Respiratory Burst / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D005353:Fibronectins; D016028:Receptors, Leukocyte-Adhesion; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides