title: 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.
abstract: Previous studies have shown that neutrophils in the circulation of patients with active systemic lupus erythematosus (SLE) are activated as judged by their increased surface expression of the beta 2-integrin CD11b/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 and LS by cytofluorographic analysis of immunofluorescent-labeled cells. Overall there was no difference between surface expression of CD11b/CD18 on neutrophils from SLE patients or controls [mean fluorescence 225 +/- 26 vs 225 +/- 13 relative fluorescence units (RFU), respectively]. However, as previously reported, neutrophils from patients with more active disease (activity score > or = 3, UCH Middlesex activity score) expressed greater CD11b/CD18 than neutrophils from controls (319 +/- 40 RFU, P < 0.03, n = 9) or from patients with less active disease (193 +/- 10 RFU, P < 0.006). Indeed, CD11b/CD18 expression correlated directly with disease activity (r = 0.54, P < 0.02). Stimulation of neutrophils ex vivo with the chemoattractant N-formyl-methionyl-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 > or = 3) increased CD11b/CD18 expression 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 < 0.003, n = 20). Surprisingly, we observed no change in LS expression on neutrophils from SLE patients compared to controls (143 +/- 14 vs 141 +/- 16 RFU, respectively) even in patients with the highest activity indices (154 +/- 21 RFU). In contrast to CD11b/CD18, there was no correlation between LS expression and disease activity (r = 0.12, P = NS). Stimulation of neutrophils reduced the expression of LS similarly in both controls and SLE patients (67 +/- 3% vs 58 +/- 4% reduction, respectively) and did not correlate with disease activity (r = 0.07, P = NS, n = 20). These results show, for the first time, that changes in CD11b/CD18 expression do not correlate with LS expression on neutrophils from patients with active SLE.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Medicine, New York University Medical Center, New York 10016.
authors.forename: Y
authors.initials: Y
authors.lastname: Molad
authors.forename: J
authors.initials: J
authors.lastname: Buyon
authors.forename: D C
authors.initials: DC
authors.lastname: Anderson
authors.forename: S B
authors.initials: SB
authors.lastname: Abramson
authors.forename: B N
authors.initials: BN
authors.lastname: Cronstein
mesh_terms: D015703:Antigens, CD / Q000097:blood / Q000502:physiology; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules / Q000097:blood / Q000502:physiology; D002630:Chemotactic Factors / Q000494:pharmacology; D005453:Fluorescence; D006801:Humans; D019041:L-Selectin; D008180:Lupus Erythematosus, Systemic / Q000097:blood*; D016177:Macrophage-1 Antigen / Q000097:blood / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D002630:Chemotactic Factors; D016177:Macrophage-1 Antigen; D019041:L-Selectin