INTRAVASCULAR NEUTROPHIL ACTIVATION IN SYSTEMIC LUPUS-ERYTHEMATOSUS (SLE) DISSOCIATION BETWEEN INCREASED EXPRESSION OF CD11B CD18 AND DIMINISHED EXPRESSION OF L-SELECTIN ON NEUTROPHILS FROM PATIENTS WITH ACTIVE SLE/

Previous studies have shown that neutrophils in the circulation of pat ients with active systemic lupus erythematosus (SLE) are activated as judged by their increased surface expression of the beta 2-integrin CD 11b/CD18. Since activation of neutrophils leads to altered expression of another adhesion molecule, L-selectin (LS), we examined neutrophils from patients with SLE for changes in the expression of CD11b/CD18 an d LS by cytofluorographic analysis of immunofluorescent-labeled cells. Overall there was no difference between surface expression of CD11b/C D18 on neutrophils from SLE patients or controls [mean fluorescence 22 5 +/- 26 vs 225 +/- 13 relative fluorescence units (RFU), respectively ]. However, as previously reported, neutrophils from patients with mor e active disease (activity score greater than or equal to 3, UCH Middl esex activity score) expressed greater CD11b/CD18 than neutrophils fro m controls (319 +/- 40 RFU, P < 0.03, n = 9) or from patients with les s active disease (193 +/- 10 RFU, P < 0.006). Indeed, CD11b/CD18 expre ssion correlated directly with disease activity (r = 0.54, P < 0.02). Stimulation of neutrophils ex vivo with the chemoattractant N-formyl-m ethionyl-leucyl-phenylalanine (100 nM) induced up-regulation of CD11b/ CD18 in cells from both SLE patients and controls (205 +/- 12% vs 239 +/- 15% of basal, respectively), but neutrophils from the most active patients (score greater than or equal to 3) increased CD11b/CD18 expre ssion less than controls (175 +/- 12% of basal, P < 0.003, n = 9). The magnitude of the stimulated increment in expression of CD11b/CD18 on neutrophils correlated inversely with SLE activity (r = -0.64, P < 0.0 03, n = 20). Surprisingly, we observed no change in LS expression on n eutrophils from SLE patients compared to controls (148 +/- 14 vs 141 /- 16 RFU, respectively) even in patients with the highest activity in dices (154 +/- 21 RFU). In contrast to CD11b/CD18, there was no correl ation between LS expression and disease activity (r = 0.12, P = NS). S timulation of neutrophils reduced the expression of LS similarly in bo th controls and SLE patients (67 +/- 3% vs 58 +/- 4% reduction, respec tively) and did not correlate with disease activity (r = 0.07, P = NS, n = 20). These results show, for the first time, that changes in CD11 b/CD18 expression do not correlate with LS expression on neutrophils f rom patients with active SLE. Moreover, since C5a and other chemoattra ctants (over a range of concentrations) stimulated changes of identica l magnitude in surface expression of CD11b/CD18 and LS, our data sugge st that the exposure of neutrophils to chemoattractants in the circula tion of patients with active SLE is not sufficient to account for all of the alterations observed in neutrophil adhesion molecules. (C) 1994 Academic Press, Inc.