Abstract:
:Human neutrophils, added to fibronectin (FN)-coated polystyrene wells and exposed to tumour necrosis factor-alpha (TNF-alpha), were found to exhibit a prolonged production of superoxide anion (O2-) after a lag period of approx 30 min. The O2- production, but not the cell adherence to FN, was completely inhibited by two MoAbs against CD18 and by a MoAb against CD11b, suggesting the involvement of CD11b-CD18 integrins in the neutrophil oxidative response. When neutrophils were induced to adhere to FN by incubation for 30 min on FN-coated surfaces and then washed to remove non-adherent cells, FN-anchored cells exhibited a rapid onset of O2- production in response to TNF-alpha. This suggests that FN primes neutrophils for the TNF-alpha-mediated respiratory burst. The O2- production by adherent neutrophils could be inhibited by anti-CD11b and anti-CD18 MoAbs only when the MoAbs were present both during the induction of adherence and during the subsequent exposure of FN-bound cells to TNF-alpha. The incapacity of MoAbs, added to neutrophils during the induction of adherence, to modify the characteristics of the subsequent neutrophil response to TNF-alpha suggests that the FN-mediated cell priming is independent of the interaction of CD11b-CD18 integrins with the FN substrate. The results are consistent with the intervention of three classes of cell receptors in the TNF-alpha-induced oxidative burst of neutrophils plated on FN: (i) neutrophil FN-binding sites, distinct from CD11b-CD18 and responsible for the cell priming; (ii) CD11b-CD18 integrins, absolutely required for permitting the cell triggering; and (iii) TNF-alpha receptors, responsible for switching on a rapid cell response in primed cells. The requirement of multiple classes of receptors for the full expression of the cell function can be envisaged as a natural precautionary measure to control the neutrophil responsiveness to TNF-alpha and, in turn, the TNF-alpha-dependent neutrophil-mediated oxidative injury at sites of inflammation.
journal_name
Clin Exp Immunoljournal_title
Clinical and experimental immunologyauthors
Dapino P,Dallegri F,Ottonello L,Sacchetti Cdoi
10.1111/j.1365-2249.1993.tb08230.xsubject
Has Abstractpub_date
1993-12-01 00:00:00pages
533-8issue
3eissn
0009-9104issn
1365-2249journal_volume
94pub_type
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