Ibuprofen inhibits adhesion-dependent neutrophil response by a glycoprotein-unrelated mechanism

The anti-inflammatory drug ibuprofen was found to inhibit neutrophil aggregation and chemotaxis, triggered by the chemotactic factor N-formyl-methionyl-leucyl-phenylalanine (FMLP). The drug did not modify the surface expression of the glycoprotein CD11b-CD18, required for both aggregation and chemotaxis. Consistent with this finding, ibuprofen did not affect the release of lactoferrin from secondary granules which contain CD11b-CD18 molecules in their membranes. As the drug failed to interfere with the neutrophil oxidant production and primary granule release, the results suggest that it acts primarily at the initial steps of the neutrophil response during inflammation, i.e. the cell recruitment at inflamed tissue sites. Moreover, the data prove that adhesion-dependent neutrophil responses required cell processes independent of CD11b-CD18 but controlled, at least in part, by ibuprofen-inhibitable pathways.