Neutrophil-derived heparin-binding protein (HBP/CAP37) deposited on endothelium enhances monocyte arrest under flow conditions.
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.
Soehnlein
Oliver
O
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Xie
Xun
X
Ulbrich
Holger
H
Kenne
Ellinor
E
Rotzius
Pierre
P
Flodgaard
Hans
H
Eriksson
Einar E
EE
Lindbom
Lennart
L
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000276:immunology; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002417:Cattle; D002460:Cell Line; D002464:Cell Migration Inhibition; D003600:Cytosol / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D008262:Macrophage Activation; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism / Q000502:physiology; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000378:metabolism*; D011485:Protein Binding
C062991:AZU1 protein, human; D000276:Adjuvants, Immunologic; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D018945:Monocyte Chemoattractant Proteins; D002118:Calcium