Amino acid sequence of CAP37, a human neutrophil granule‐derived antibacterial and monocyte‐specific chemotactic glycoprotein structurally similar to neutrophil elastase

Pohl, Jan; Pereira, H. Anne; Martin, Nancy M.; Spitznagel, John K.

doi:10.1016/0014-5793(90)80484-z

Cited by 71 publications

(62 citation statements)

References 31 publications

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“…Azurocidin (17) and cationic antimicrobial peptides (ref. 18; Fig. 3B) were observed in M2 and M3 subtypes of AML and in normal neutrophils, but not in M1 subtype.…”

Section: Resultsmentioning

confidence: 88%

Proteomic Analysis of Human Acute Leukemia Cells

Cui

Wang

et al. 2004

Clinical Cancer Research

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Purpose: French-American-British (FAB) classification of acute leukemia with genetic heterogeneity is important for treatment and prognosis. However, the distinct protein profiles that contribute to the subtypes and facilitate molecular definition of acute leukemia classification are still unclear.Experimental Design: The proteins of leukemic cells from 61 cases of acute leukemia characterized by FAB classification were separated by two-dimensional electrophoresis, and the differentially expressed protein spots were identified by both matrix-assisted laser desorption/ioniza- tion-time-of-flight-mass spectrometry (MALDI-TOF-MS) and tandem electrospray ionization MS (ESI-MS/MS).Results: The distinct protein profiles of acute leukemia FAB types or subtypes were successfully explored, including acute myeloid leukemia (AML), its subtypes (M2, M3, and M5) and acute lymphoid leukemia (ALL), which were homogeneous within substantial samples of the respective subgroups but clearly differed from all other subgroups. We found a group of proteins that were highly expressed in M2 and M3, rather than other subtypes. Among them, myeloidrelated proteins 8 and 14 were first reported to mark AML differentiation and to differentiate AML from ALL. Heat shock 27 kDa protein 1 and other proteins that are highly expressed in ALL may play important roles in clinically distinguishing AML from ALL. Another set of proteins up-regulated was restricted to granulocytic lineage leukemia. High-level expression of NM23-H1 was found in all but the M3a subtype, with favorable prognosis.Conclusions: These data have implications in delineating the pathways of aberrant gene expression underlying the pathogenesis of acute leukemia and could facilitate molecular definition of FAB classification. The extension of the present analysis to currently less well-defined acute leukemias will identify additional subgroups.

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“…Azurocidin (17) and cationic antimicrobial peptides (ref. 18; Fig. 3B) were observed in M2 and M3 subtypes of AML and in normal neutrophils, but not in M1 subtype.…”

Section: Resultsmentioning

confidence: 88%

Proteomic Analysis of Human Acute Leukemia Cells

Cui

Wang

et al. 2004

Clinical Cancer Research

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“…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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“…Heparin-binding protein (HBP), also termed CAP37 [1] and azurocidin [2], is a human neutrophil-derived serine protease homologue exhibiting 45% sequence identity to neutrophil elastase, and 30-37% identity to several other granule serine proteases [3,4]. Despite these similarities, HBP is devoid of proteolytic activity because the active site residues serine and histidine have been replaced.…”

Section: Introductionmentioning

confidence: 99%