CAP37, a neutrophil-derived inflammatory mediator, augments leukocyte adhesion to endothelial monolayers

The Journal of Immunology

Xie²,

Ulbrich³

et al. 2005

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 Ca2+ 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.

Section: Discussioncontrasting

confidence: 70%

Neutrophil-Derived Heparin-Binding Protein (HBP/CAP37) Deposited on Endothelium Enhances Monocyte Arrest under Flow Conditions

The Journal of Immunology

Xie²,

Ulbrich³

et al. 2005

“…1B). As shown by Lee et al [31], azurocidin enhances the expression of E-selectin, ICAM-1, and VCAM-1, which is associated with an increased adhesion of PMN and monocytes. Moreover, it has been suggested that azurocidin is produced by EC themselves upon cytokine stimulation [30].…”

Section: Azurocidin Induces Recruitment Of Monocytesmentioning

confidence: 71%

Neutrophil-derived azurocidin alarms the immune system

Journal of Leukocyte Biology

Lindbom

2008

102

100

Azurocidin (heparin-binding protein/ cationic antimicrobial protein of 37 kD) is a protein that is mobilized rapidly from emigrating polymorphonuclear leukocytes (PMN). Initially, this inactive serine protease was recognized for its antimicrobial effects. However, it soon became apparent that azurocidin may act to alarm the immune system in different ways and thus serve as an important mediator during the initiation of the immune response. Azurocidin, released from PMN secretory vesicles or primary granules, acts as a chemoattractant and activator of monocyte and macrophages. The functional consequence is enhancement of cytokine release and bacterial phagocytosis, allowing for a more efficient bacterial clearance. Leukocyte activation by azurocidin is mediated via ␤ 2 -integrins, and azurocidin-induced chemotaxis is dependent on formyl-peptide receptors. In addition, azurocidin activates endothelial cells leading to vascular leakage and edema formation. For these reasons, targeting azurocidin release and its actions may have therapeutic potential in inflammatory disease conditions. J. Leukoc. Biol. 85: 344 -351; 2009.

“…Lee et al have shown that azurocidin enhances the expression of VCAM-1 and ICAM-1, resulting in enhanced adhesion of human monocytes. 49 Similarly, proteinase-3 induces expression of these 2 CAMs resulting in enhanced adhesion of PMNs and monocytes to isolated endothelial cells 50 (Figure 2).…”

Section: Contribution Of Pmn Granule Proteins To Monocyte Recruitmentmentioning

confidence: 96%

Mechanisms underlying neutrophil-mediated monocyte recruitment

Lindbom

Weber

2009

Blood

241

197

Extravasation of polymorphonuclear leukocytes (PMNs) to the site of inflammation precedes a second wave of emigrating monocytes. That these events are causally connected has been established a long time ago. However, we are now just beginning to understand the molecular mechanisms underlying this cellular switch, which has become even more complex considering the emergence of monocyte subsets, which are affected differently by signals generated from