Antibacterial Activity of Antileukoprotease

Department of Pulmonology, Leiden University Hospital, The Netherlands.
Infection and Immunity (Impact Factor: 3.73). 12/1996; 64(11):4520-4.
Source: PubMed


Antileukoprotease (ALP), or secretory leukocyte proteinase inhibitor, is an endogenous inhibitor of serine proteinases that is present in various external secretions. ALP, one of the major inhibitors of serine proteinases present in the human lung, is a potent reversible inhibitor of elastase and, to a lesser extent, of cathepsin G. In equine neutrophils, an antimicrobial polypeptide that has some of the characteristics of ALP has been identified (M. A. Couto, S. S. L. Harwig, J. S. Cullor, J. P. Hughes, and R. I. Lehrer, Infect. Immun. 60:5042-5047, 1992). This report, together with the cationic nature of ALP, led us to investigate the antimicrobial activity of ALP. ALP was shown to display marked in vitro antibacterial activity against Escherichia coli and Staphylococcus aureus. On a molar basis, the activity of ALP was lower than that of two other cationic antimicrobial polypeptides, lysozyme and defensin. ALP comprises two homologous domains: its proteinase-inhibitory activities are known to be located in the second COOH-terminal domain, and the function of its first NH2-terminal domain is largely unknown. Incubation of intact ALP or its isolated first domain with E. coli or S. aureus resulted in killing of these bacteria, whereas its second domain displayed very little antibacterial activity. Together these data suggest a putative antimicrobial role for the first domain of ALP and indicate that its antimicrobial activity may equip ALP to contribute to host defense against infection.

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    • "SLPI inhibits a wide variety of proteases including neutrophil elastase (NE), cathepsin G, trypsin, chymotrypsin, chymase, and tryptase [11]. In addition, research suggests that SLPI has antimicrobial effects and is capable of inhibiting both Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli) bacterial growth [12] [13] as well as inhibiting HIV viral replication in monocytic cells [14] [15]. "
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    ABSTRACT: Secretory Leukocyte Protease Inhibitor (SLPI) is a serine protease inhibitor produced by epithelial and myeloid cells with anti-inflammatory properties. Research has shown that SLPI exerts its anti-inflammatory activity by directly binding to NF- κ B DNA binding sites and, in so doing, prevents binding and subsequent transcription of proinflammatory gene expression. In the current study, we demonstrate that SLPI can inhibit TNF- α -induced apoptosis in U937 cells and peripheral blood monocytes. Specifically, SLPI inhibits TNF- α -induced caspase-3 activation and DNA degradation associated with apoptosis. We go on to show that this ability of SLPI to inhibit apoptosis is not dependent on its antiprotease activity as antiprotease deficient variants of SLPI can also inhibit TNF- α -induced apoptosis. This reduction in monocyte apoptosis may preserve monocyte function during inflammation resolution and promote infection clearance at mucosal sites.
    Journal of Immunology Research 08/2015; 2015(2):507315. DOI:10.1155/2015/507315 · 2.93 Impact Factor
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    • "Examples include dermcidin and histone H4, which are expressed in eccrine sweat glands and by sebocytes, respectively, and secreted to the skin (Rieg et al., 2004; Lee et al., 2009). Moreover, secretory leukocyte protease inhibitor (SLPI) and elafin/elastase-specific inhibitor (ESI)/skin-derived antileukoprotease (SKALP) kill S. aureus (Hiemstra et al., 1996; Simpson et al., 1999), and the proteins can be induced in keratinocytes/epidermis (Bando et al., 2007). Another class of putative relevant antimicrobial proteins is the peptidoglycan recognition proteins (PGRPs; Dziarski and Gupta, 2010). "
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    ABSTRACT: Staphylococcus aureus may cause serious skin and soft tissue infections, deep abscesses, endocarditis, osteomyelitis, pneumonia, and sepsis. S. aureus persistently colonizes 25-30% of the adult human population, and S. aureus carriers have an increased risk for infections caused by the bacterium. The major site of colonization is the nose, i.e., the vestibulum nasi, which is covered with ordinary skin and hair follicles. Several host and microbe determinants are assumed to be associated with colonization. These include the presence and expression level of bacterial adhesins, which can adhere to various proteins in the extracellular matrix or on the cellular surface of human skin. The host expresses several antimicrobial peptides and lipids. The level of β-defensin 3, free sphingosine, and cis-6-hexadecenoic acid are found to be associated with nasal carriage of S. aureus. Other host factors are certain polymorphisms in Toll-like receptor 2, mannose-binding lectin, C-reactive protein, glucocorticoid-, and vitamin D receptor. Additional putative determinants for carriage include genetic variation and expression of microbial surface components recognizing adhesive matrix molecules and their interaction partners, as well as variation among humans in the ability of recognizing and responding appropriately to the bacteria. Moreover, the available microflora may influence the success of S. aureus colonization. In conclusion, colonization is a complex interplay between the bacteria and its host. Several bacterial and host factors are involved, and an increased molecular understanding of these are needed.
    Frontiers in Cellular and Infection Microbiology 05/2012; 2(56):56. DOI:10.3389/fcimb.2012.00056 · 3.72 Impact Factor
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    • "Besides maturation in the epididymis, factors present in the secretions of the prostate and seminal vesicles are also thought to be involved in production of functional spermatozoa [2], [3], [4]. Epididymal and seminal vesicle fluid consists of a wide variety of proteins [5] which includes defensins [6], [7], lipocalins [8], cathelicidins [9], members of the sperm associated antigen 11 family [10], protease inhibitors [11], [12], [13], inhibitors of complement lysis [14], [15], lysozymes [16], [17] and the cysteine rich proteins such as CRISPs [18] and members of the PATE family [19], [20], [21], [22]. "
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    ABSTRACT: The cysteine rich prostate and testis expressed (Pate) proteins identified till date are thought to resemble the three fingered protein/urokinase-type plasminogen activator receptor proteins. In this study, for the first time, we report the identification, cloning and characterization of rat Pate gene cluster and also determine the expression pattern. The rat Pate genes are clustered on chromosome 8 and their predicted proteins retained the ten cysteine signature characteristic to TFP/Ly-6 protein family. PATE and PATE-F three dimensional protein structure was found to be similar to that of the toxin bucandin. Though Pate gene expression is thought to be prostate and testis specific, we observed that rat Pate genes are also expressed in seminal vesicle and epididymis and in tissues beyond the male reproductive tract. In the developing rats (20-60 day old), expression of Pate genes seem to be androgen dependent in the epididymis and testis. In the adult rat, androgen ablation resulted in down regulation of the majority of Pate genes in the epididymides. PATE and PATE-F proteins were found to be expressed abundantly in the male reproductive tract of rats and on the sperm. Recombinant PATE protein exhibited potent antibacterial activity, whereas PATE-F did not exhibit any antibacterial activity. Pate expression was induced in the epididymides when challenged with LPS. Based on our results, we conclude that rat PATE proteins may contribute to the reproductive and defense functions.
    PLoS ONE 03/2012; 7(3):e32633. DOI:10.1371/journal.pone.0032633 · 3.23 Impact Factor
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