title: A peptide derived from neutrophil inhibitory factor (NIF) blocks neutrophil adherence to endothelial cells.
abstract: OBJECTIVE
  Peptides derived from neutrophil inhibitory factor (NIF), a known antagonist of Mac-1, were evaluated as inhibitors of neutrophil adherence.
  
  
  METHODS
  In vitro assays of adherence employed: 1) human polymorphonuclear cells (PMN), 2) human umbilical vein endothelial cells (HUVEC), and 3) CHO cells expressing ICAM-1 (CHO-ICAM cells).
  
  
  METHODS
  Cells, pretreated with NIF-derived peptides (0.1-100 microM) for 10 minutes, were permitted to adhere for 20 min in the continued presence of peptide.
  
  
  METHODS
  Cell-based assays: 1) PMN adherence to HUVEC, 2) PMN adhesion to immobilized human serum proteins, and 3) adherence of CHO-ICAM cells to immobilized Mac-1.
  
  
  RESULTS
  A NIF-derived peptide of 29 amino acids blocked PMN adherence to HUVEC, but behaved somewhat differently than the parent NIF protein. NIF specifically antagonized Mac-1 dependent adherence, but the peptide blocked neutrophil adherence that was dependent upon both Mac-1 and LFA-1 integrins. CHO-ICAM adherence to Mac-1 was blocked by NIF, but not by the peptide. Binding studies with NIF and the peptide indicate that the molecules bind to different sites.
  
  
  CONCLUSIONS
  A peptide derived from NIF blocks PMN adherence but, unlike NIF, the mechanism of action is not mediated by direct antagonism Mac-1.
authors.affiliation: Scios Inc., Sunnyvale, CA 94086, USA.
authors.forename: K
authors.initials: K
authors.lastname: Madden
authors.forename: J
authors.initials: J
authors.lastname: Janczak
authors.forename: G
authors.initials: G
authors.lastname: McEnroe
authors.forename: D
authors.initials: D
authors.lastname: Lim
authors.forename: T
authors.initials: T
authors.lastname: Hartman
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Stanton
mesh_terms: D000595:Amino Acid Sequence; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D006023:Glycoproteins / Q000494:pharmacology*; D015801:Helminth Proteins / Q000494:pharmacology*; D006801:Humans; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D006023:Glycoproteins; D015801:Helminth Proteins; D008565:Membrane Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C086581:NIF protein, Ancylostoma caninum