Neutrophil-derived heparin-binding protein (HBP/CAP37) deposited on endothelium enhances monocyte arrest under flow conditions

J Immunol. 2005 May 15;174(10):6399-405. doi: 10.4049/jimmunol.174.10.6399.


In acute inflammation, infiltration of neutrophils often precedes a second phase of monocyte invasion, and data in the literature suggest that neutrophils may directly stimulate mobilization of monocytes via neutrophil granule proteins. In this study, we present a role for neutrophil-derived heparin-binding protein (HBP) in monocyte arrest on endothelium. Adhesion of neutrophils to bovine aorta endothelial cells (ECs) or HUVEC-triggered secretion of HBP and binding of the protein to the EC surface. Blockade of neutrophil adhesion by treatment with a mAb to CD18 greatly reduced accumulation of HBP. In a flow chamber model, immobilized recombinant HBP induced arrest of human monocytes or monocytic Mono Mac 6 (MM6) cells to activated EC or plates coated with recombinant adhesion molecules (E-selectin, P-selectin, VCAM-1). However, immobilized recombinant HBP did not influence arrest of neutrophils or lymphocytes. Treatment of MM6 cells with recombinant HBP evoked a rapid and clear-cut increase in cytosolic free Ca(2+) that was found to be critical for the HBP-induced monocyte arrest inasmuch as pretreatment with the intracellular calcium chelating agent BAPTA-AM abolished the evoked increase in adhesion. Thus, secretion of a neutrophil granule protein, accumulating on the EC surface and promoting arrest of monocytes, could contribute to the recruitment of monocytes at inflammatory loci.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / physiology*
  • Animals
  • Antimicrobial Cationic Peptides
  • Blood Proteins / metabolism
  • Blood Proteins / physiology*
  • Calcium / metabolism
  • Calcium Signaling / immunology
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Cattle
  • Cell Line
  • Cell Migration Inhibition*
  • Cytosol / metabolism
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / pathology*
  • Humans
  • Intracellular Fluid / metabolism
  • Macrophage Activation
  • Monocyte Chemoattractant Proteins / metabolism
  • Monocyte Chemoattractant Proteins / physiology
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Monocytes / pathology
  • Neutrophil Infiltration / immunology*
  • Neutrophils / metabolism*
  • Protein Binding


  • AZU1 protein, human
  • Adjuvants, Immunologic
  • Antimicrobial Cationic Peptides
  • Blood Proteins
  • Carrier Proteins
  • Monocyte Chemoattractant Proteins
  • Calcium