CAP 37, A 37 kD human neutrophil granule cationic protein shares homology with inflammatory proteinases

Pereira, H. Anne; Spitznagel, John K.; Pohl, Jan; Wilson, Douglas E.; Morgan, John G.; Palings, Ilona; Larrick, James W.

doi:10.1016/0024-3205(90)90104-y

Cited by 32 publications

(28 citation statements)

References 15 publications

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“…Upon these initial events of PMN extravasation, the content of rapidly mobilizable, secretory vesicles is discharged in the secluded compartment between the PMN and the endothelial cell (EC). Azurocidin, a major component of secretory vesicles, is strongly, positively charged [20] and may thus accumulate on the negatively charged EC surface. In this way, azurocidin becomes immobilized on the endothelium and thereby exposed to cells in the blood flow [23] (Fig.…”

Section: Azurocidin Induces Recruitment Of Monocytesmentioning

confidence: 99%

“…There, the chemotactic effect of azurocidin on monocytes vanished when the cells were pretreated with pertussis toxin (PTx), indicative of the involvement of a Giprotein-coupled receptor (GiPCR) [33]. Azurocidin shares strong homology with the serine proteases elastase, proteinase-3, and cathepsin G [20]. The latter has been shown to be chemotactic for monocytes in a PTx-sensitive manner.…”

Section: Azurocidin Mediates Its Effects On Leukocytes Via ␤ 2 -Integmentioning

confidence: 99%

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Neutrophil-derived azurocidin alarms the immune system

Soehnlein

Lindbom

2008

Journal of Leukocyte Biology

101

100

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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.

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Section: Azurocidin Induces Recruitment Of Monocytesmentioning

confidence: 99%

Section: Azurocidin Mediates Its Effects On Leukocytes Via ␤ 2 -Integmentioning

confidence: 99%

Neutrophil-derived azurocidin alarms the immune system

Soehnlein

Lindbom

2008

Journal of Leukocyte Biology

101

100

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“…Levels of endotoxin in the cathepsin G samples were determined to be Ͻ 0.1 endotoxin units/g following passage over a Detoxi-Gel Affinity Pak column (Pierce, Rockford, IL) to remove contaminating endotoxin. Cathepsin G was selected since it is a human neutrophil granule-derived protein with similar molecular weight to CAP37 and almost 35% sequence homology to CAP37 (Pereira et al, 1990a). Since CAP37 is a known LPS binding protein (Pereira et al, 1993), we included additional controls in which polymyxin B (2 g/ml, Sigma) was added to test samples containing CAP37, LPS, and cathepsin G. This control was included to confirm that the functional properties attributed to CAP37 in our studies were not due to endotoxin contamination of the rCAP37 preparation.…”

Section: Morphologic Determination Of Microglial Activationmentioning

confidence: 99%

“…Over the past decade, we have identified and characterized a novel cationic antimicrobial protein of M r 37 kDa (CAP37) and demonstrated its role as a pleiotropic inflammatory mediator in the systemic circulation (Pereira et al, 1990a;Pohl et al, 1990;Morgan et al, 1991). It is a key mediator of monocyte (Pereira, 1995) and endothelial cell functions (Pereira, 2001) and promotes monocyte chemotaxis (Pereira et al, 1990b), adhesion of monocytes to endothelial cells, and activates endothelial cell protein kinase C, a critical second messenger (Pereira et al, 1996a).…”

Section: Introductionmentioning

confidence: 99%

Activation of microglia: A neuroinflammatory role for CAP37

Pereira

Ruan

Kumar³

2002

Glia

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Recent evidence suggests that inflammation and immune function in the central nervous system (CNS) may play a considerable role in the progression of many neurodegenerative diseases. It is known that microglia, the CNS equivalent of peripheral blood monocytes, may be instrumental in causing neurotoxicity. However, the mediator(s) that activates microglia to produce toxic substances that orchestrate cell death has yet to be elucidated. We have identified a novel inflammatory molecule, cationic antimicrobial protein of molecular weight 37 kDa (CAP37), to the brains of patients dying from Alzheimer's disease. CAP37 is known to be a potent activator and regulator of monocyte function in the systemic circulation. We hypothesize that CAP37, a mediator previously shown to recruit and activate monocytes in the systemic circulation, may also play a role in CNS inflammation by modulating microglial function. Here we demonstrate that CAP37 is a chemoattractant for microglia and that CAP37-treated microglia express class II major histocompatibility antigens and produce proinflammatory cytokines and chemokines. We conclude that CAP37 has the ability to activate microglial cells and suggest that it has the potential to serve as a neuroinflammatory molecule. GLIA 41:64 -72, 2003.

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“…However, of note and exceptional to the homology, is a two amino acid substitutionpHis + Ser and Ser + Gly-in the active site triad of serine proteases. Thu3, azurocidin exhibits the structural features of a 'sterile' enzyme, and indeed it has been demonstrated that azurocidin is unable to bind 3H-diisopropylfluorophosphate and to cleave synthetic substrate specific to serine proteases [13]. A stereopicture of azurocidin based on the elastase model reveals that the amino-terminal domain is rich in basic residues, and that these positive changes are exposed on the surface, as may be expected from a PI value of 9.2 [12].…”

Section: Discussionmentioning

confidence: 95%

Azurocidin is a novel antigen for anti-neutrophil cytoplasmic autoantibodies (ANCA) in systemic vasculitis

Zhao

Lockwood

1996

Clinical and Experimental Immunology

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SUMMARYWe isolated a 27-kD protein using cation exchange chromatography from an acid extract of neutrophil granules. N-terminal amino acid sequence analysis of the first 10 residues showed that this protein is azurocidin, a member of the family of neutral serine proteinase found in the neutrophil, which shares amino acid sequence homology with the three other neutral serine proteinases, elastase, proteinase 3 (PR3) and cathepsin G, but unlike them is without proteolytic activity. To test whether, in addition to these proteases, azurocidin might be a target for the humoral autoimmune responses associated with human vasculitis, 185 indirect immunofluorescence (1IF)-positive ANCA sera, made up of four groups of sera with specificities for PR3 (n = 37), myeloperoxidase (MPO; n = 50), bactericidal/permeability-increasing protein (BPI; n = 41) and sera that recognized none of them (triple negative, n = 57), and 46 normal sera were screened for IgG anti-azurocidin antibodies using an ELISA incorporating purified azurocidin. Twenty of the 185 IIF-positive sera and 2/46 normal sera displayed reactivity with azurocidin. Positive sera could blot the 27-kD band by Western blot analysis. Further study of the 20 positive sera revealed that: (i) 10 also had autoreactivity for MPO, of which six additionally recognized lactoferrin; (ii) two had reactivity with BPI; (iii) the remaining eight sera were positive only for azurocidin. All 20 sera were from patients with systemic vasculitis, and four of the six sera with triple reactivity (for azurocidin, MPO and lactoferrin) were from patients with hydralazine-induced vasculitis. We concluded that: (i) azurocidin is a novel ANCA antigen; (ii) anti-azurocidin antibodies from a subgroup of patients might represent the consequence of a drug-induced multi-clone activation.

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CAP 37, A 37 kD human neutrophil granule cationic protein shares homology with inflammatory proteinases

Cited by 32 publications

References 15 publications

Neutrophil-derived azurocidin alarms the immune system

Neutrophil-derived azurocidin alarms the immune system

Activation of microglia: A neuroinflammatory role for CAP37

Azurocidin is a novel antigen for anti-neutrophil cytoplasmic autoantibodies (ANCA) in systemic vasculitis

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