M. Nagata et al., EOSINOPHIL ADHESION TO VASCULAR CELL-ADHESION MOLECULE-1 ACTIVATES SUPEROXIDE ANION GENERATION, The Journal of immunology, 155(4), 1995, pp. 2194-2202
Adhesion to the adhesion protein, VCAM-1, on vascular endothelium is p
roposed to be an important factor in the selective accumulation of eos
inophils at sites of allergic inflammation. To determine whether eosin
ophil adhesion to VCAM-1 is also associated with an alteration of eosi
nophil function, human peripheral blood eosinophils were isolated from
allergic donors and incubated in VCAM-1-coated wells. Spontaneous adh
erence of isolated eosinophils to VCAM-1-coated wells was greater than
cells incubated in FCS-treated control wells (38.0 +/- 1.6% vs 17.1 /- 1.9%, n = 16, p < 0.0001). In addition, eosinophils incubated in VC
AM-1-coated wells spontaneously generated modest but significant amoun
ts of superoxide anion (O-2(-); 2.0 +/- 1.3 vs 0.5 +/- 0.5 nmol/5 x 10
(5) cells, n = 9, p = 0.029). Moreover, when 100 nM FMLP was added to
eosinophils in the presence of VCAM-1, significantly greater O-2(-) ge
neration occurred (7.2 +/- 0.9 vs 5.4 +/- 1.0 (FCS control) nmol/5 x 1
0(5) cells, n = 9, p = 0.009). Adhesion, as well as the spontaneous an
d enhanced O-2(-) generation to FMLP activation, was blocked by the mo
noclonal anti-alpha(4) integrin Ab, HP 1/2, implying involvement of an
alpha(4) integrin-VCAM-1 interaction. In contrast, the anti-CD18 mAb,
L130, inhibited the spontaneous and enhanced O-2(-) generation to FML
P without affecting adhesion, suggesting an involvement of CD18 molecu
le(s) only in VCAM-1-enhanced respiratory burst. Finally, 1 mu M genis
tein, a tyrosine kinase inhibitor, suppressed the VCAM-1-enhancing eff
ect on eosinophil O-2(-) generation and VCAM-1-induced tyrosine phosph
orylation, suggesting a role for tyrosine phosphorylation in this eosi
nophil functional up-regulation. Our observations suggest that eosinop
hil adhesion to VCAM-1 may be an important step in determining the eve
ntual functional activity of these cells as they migrate from the circ
ulation to the airways and contribute to the allergic inflammatory pro
cess.