The anti-inflammatory peptides, antiflammins, regulate the expression of adhesion molecules on human leukocytes and prevent neutrophil adhesion to endothelial cells

Antiflammin-1 and antiflammin-2 are nonapeptides corresponding to the regio n of highest similarity between glucocorticoid-inducible proteins lipocorti n-1 and uteroglobin. We have studied whether antiflammins could affect expr ession of adhesion molecules on human leukocytes and coronary artery endoth elial cells (HCAEC) and binding of neutrophils (PMNs) to HCAEC. Although ne ither antiflammin-1 nor antiflammin-2 affected expression of adhesion molec ules on resting PMNs, monocytes, and lymphocytes in whole blood, they atten uated changes in L-selectin and CD11/CD18 expression evoked by platelet-act ivating factor or interleukin-8 with IC50 values of 4-20 mu mol/l. The maxi mum inhibition was similar to those seen with human recombinant lipocortin- 1 (100 mu g/ml). Unlike,dexamethasone (100 nnol/l), the antiflammins had li ttle effect on LPS-stimulated expression of E-selectin and ICAM-1 on HCAEC. Consistently, culture of HCAEC with dexamethasone, but not with antiflammi ns, decreased PMN binding to endothelial cells. Preincubation of PMNs with antiflammins markedly decreased their adhesion to LPS-activated HCAEC. Inhi bition of adhesion was additive with function blocking anti-E-selectin and anti-L-selectin antibodies, but was not additive with anti-CD18 antibody. T hese results show that antiflammins inhibit PMN adhesion to HCAEC by attenu ating. activation-induced upregulation of CD11/CD18 expression on leukocyte s, and suggest that antiflammins may represent a novel therapeutic approach in blocking leukocyte trafficking in host defense and inflammation.