Inhibition of in vivo neutrophil transmigration by a novel humanized anti-CD11/CD18 monoclonal antibody.
Leukocyte adhesion receptors, including the beta-integrin (CD11/CD18) family, play an important role in inflammation via their regulatory effects on leukocyte adhesion, transmigration, and function. A randomized, placebo-controlled, double-blind study was conducted in healthy volunteers to evaluate the in vivo effects of a humanized anti-CD11/CD18 monoclonal antibody, Hu23F2G, on leukocyte activation and transmigration. Neutrophil migration to a site of cutaneous inflammation in vivo, as measured by the skin chamber technique, was significantly reduced in subjects 24 hours after Hu23F2G administration. At 96 hours, neutrophil migration was not significantly different in subjects who received Hu23F2G or placebo. In contrast, delayed-type hypersensitivity (DTH) testing, which involves activation and migration of T lymphocytes and macrophages, was unaffected by the Hu23F2G treatment. These responses to Hu23F2G in vivo are similar to the clinical phenotype of leukocyte adhesion deficiency (LAD) type 1, a congenital disorder of CD18 deficiency. The in vivo properties of Hu23F2G suggest therapeutic potential for use in the treatment of acute non-infectious inflammatory disorders mediated predominantly by neutrophils.
Liles
W C
WC
Department of Medicine, University of Washington School of Medicine, Seattle 98195-6422, USA.
Dale
D C
DC
Price
T H
TH
Gaviria
J M
JM
Turner
T
T
Saoud
J
J
Frumkin
L R
LR
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D018845:CD11 Antigens / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D015194:Diffusion Chambers, Culture; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology / Q000502:physiology*; D012449:Safety
D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D018821:CD18 Antigens