Abstract
We previously described the requirement of tumour necrosis factor-alpha (TNF-α) and the role of β2 integrins in the Fc-gamma receptor IIa (FcγRIIa)-mediated mechanism of neutrophil activation by antiproteinase-3 (anti-PR3) or anti-myeloperoxidase (anti-MPO) antibodies. In the present study, we assessed the involvement of FcγRIIIb by studying the respiratory burst activation of completely FcγRIIIb-deficient neutrophils primed by TNF-α and exposed to anti-PR3 or anti-MPO. Activation of the NADPH oxidase occurred normally in these neutrophils, which indicates that engagement of FcγRIIIb is not essential in our model. Experiments performed with neutrophils from severe leucocyte adhesion deficiency (LAD) patients confirmed that β2 integrins play a pivotal role in this activation. We next studied whether adhesion per se, β2-integrin-mediated adhesion, or β2-integrin ligation without adhesion is necessary or sufficient for this activation. Anti-PR3 or anti-MPO induced an FcγRIIa-dependent burst in TNF-primed neutrophils incubated in wells coated with poly-L-lysine, known to induce β2-integrin-independent adhesion, but this reaction was still inhibited by blocking CD18 antibodies. In a system with granulocyte-macrophage colony-stimulating factor (GM-CSF)-primed neutrophils, which did not enhance adhesion, we measured a similar activation by anti-PR3 or anti-MPO and inhibition by CD18. We also noticed that treatment with the β 2-integrin-activating CD18 MoAb KIM185 per se is insufficient for neutrophil activation by anti-PR3 or anti-MPO. We therefore conclude that ligation of β2 integrins rather than adherence per se is essential for this activation, and that TNF-α or GM-CSF is needed for priming but not for adherence.
Original language | English |
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Pages (from-to) | 344-350 |
Number of pages | 7 |
Journal | Clinical and experimental immunology |
Volume | 134 |
Issue number | 2 |
DOIs | |
Publication status | Published - Nov 2003 |
Keywords
- ANCA
- Fcγreceptors
- Neutrophil activation
- Vasculitis
- β integrins