Neutrophil influx into an inflammatory site inhibited by a soluble homing receptor-IgG chimaera.
Neutrophil-mediated inflammation is involved in a number of human clinical manifestations, including the adult respiratory distress syndrome, multi-organ failure and reperfusion injury. One way of inhibiting this type of inflammatory response would be to block competitively the adhesive interactions between neutrophils and the endothelium adjacent to the inflamed region. The lectin-containing murine adhesion molecule gp90MEL, the homing receptor, is found on all leukocytic cells, including neutrophils. MEL 14, a monoclonal antibody directed against this adhesion molecule, blocks lymphocyte traffic to lymph nodes and extravasation of neutrophils from blood to inflammatory sites. Here we show that administration to mice of a soluble immunoglobulin chimaera containing the murine homing receptor extracellular domain significantly decreases the number of neutrophils that migrate to the peritoneum in response to the inflammatory irritant thioglycollate. These results indicate that soluble forms of a single type of adhesion molecule, the homing receptor, could be clinically effective compounds for the inhibition of neutrophil-mediated inflammation.
Watson
S R
SR
Department of Immunobiology, Genetech, South San Francisco, California 94080.
Fennie
C
C
Lasky
L A
LA
D000818:Animals; D000911:Antibodies, Monoclonal; D002634:Chemotaxis, Leukocyte; D007074:Immunoglobulin G / Q000235:genetics; D007249:Inflammation / Q000503:physiopathology*; D008214:Lymphocytes / Q000502:physiology; D051379:Mice; D009504:Neutrophils / Q000502:physiology*; D010529:Peritoneal Cavity / Q000166:cytology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D012995:Solubility
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D016201:Receptors, Lymphocyte Homing; D011993:Recombinant Fusion Proteins