In vivo neutrophil recruitment by granulocyte chemotactic protein-2 is assisted by gelatinase B/MMP-9 in the mouse

Granulocyte chemotactic protein-2 (GCP-2) of the mouse is a potent neutroph il chemotactic and activating factor in vitro and in vivo. Gelatinase B/mat rix metalloproteinase-9 is released from neutrophils within 1 h after stimu lation with GCP-2. In vitro neutrophil chemotaxis by GCP-2 was not impaired by specific inhibitory monoclonal antibodies (mAb) against gelatinase B, i ndicating that gelatinase B is not involved in chemotaxis of neutrophils th rough polycarbonate filters. To investigate if gelatinase B degranulation i s involved in in vivo cell migration toward GCP-2, experiments were perform ed with gelatinase B knockout mice, When mouse GCP-2 was injected intraderm ally in mice, a dose-dependent neutrophil chemotactic response was observed , and this cell migration was significantly impaired in young mice by genet ic gelatinase B knockout. In adult vs. young gelatinase B-deficient mice, s uch compensatory mechanisms as higher basal neutrophil counts and less impa irment of chemotaxis toward local GCP-2 injection were observed. These expe riments prove the concept that gelatinase B release under pressure of GCP-2 is a relevant, but not exclusive, effector mechanism of neutrophil chemota xis in vivo and that known mechanisms, other than the release of gelatinase B, allow for a full-blown chemotactic response and compensate for gelatina se B deficiency in adult life in the mouse.