Listericidal activity of human neutrophil cathepsin G

Alford, Charlotte; Amaral, Elizabeth; Campbell, Priscilla A.

doi:10.1099/00221287-136-6-997

Cited by 19 publications

(9 citation statements)

References 15 publications

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“…These same investigators have recalled attention to the bactericidal activity of serine proteinases from PMNL, proteins which were among the earliest granule proteins analyzed for this biological activity (28,29). Cathepsin G has been the most active serine proteinase in this regard, but enzyme activity was not required for killing of any of the bacteria studied thus far (1,28,(38)(39)(40)(41). We present evidence * Corresponding author.…”

mentioning

confidence: 77%

“…This at least suggests that hydrolysis of a bacterial target is not directly involved in killing of P. aeruginosa by cathepsin G. Nevertheless, an intact active site is required for killing, and this result is in sharp contrast to an earlier study with P. aeruginosa (28), which showed that the bactericidal activity of cathepsin G was not abolished by heat inactivation of the enzyme. The bactericidal activity of cathepsin G toward Neisseria gonor-rhoeae (39,41), E. coli (28), Staphylococcus aureus (28,38), and Listeria monocytogenes (1) is also reported to be independent of its proteinase activity, from studies with heatinactivated (1,28,39) and DFP-treated (38,41) protein. Two peptides of cathepsin G which retain bactericidal activity toward N. gonorrhoeae have been isolated (3).…”

Section: Discussionmentioning

confidence: 99%

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Comparison of granule proteins from human polymorphonuclear leukocytes which are bactericidal toward Pseudomonas aeruginosa

1991

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Killing of Pseudomonas aeruginosa by a 55-kDa bactericidal protein (BP 55), a 30-kDa protein (BP 30), cathepsin G, elastase, and proteinase 3 has been compared. P. aeruginosa was resistant to killing by elastase and proteinase 3. BP 55 at a 50% lethal dose (LD50) of 0.23 ,ug of protein per 5 x 106 bacteria per ml killed P. aeruginosa and was far more active than BP 30 and cathepsin G. The LD5s of BP 30 and cathepsin G were 16.9 and 28.3 ,ug of protein per 5 x 106 bacteria per ml, respectively. Preincubation of BP 55 or BP 30 with lipopolysaccharide (LPS) from P. aeruginosa inhibited bactericidal activity. The N-terminal amino acid sequence of BP 55 and BP 30 revealed no relationship between the two proteins. However, a monoclonal antibody (AHN-15) reacted with both proteins by Western immunoblot. The bactericidal activity of cathepsin G toward P. aeruginosa appeared to be dependent on the availability of the active site of the enzyme; bactericidal activity was inhibited by phenylmethylsulfonyl fluoride (PMSF) and by the specific cathepsin G inhibitor, Z-Gly-Leu-Phe-CH2Cl. The enzyme and bactericidal activities of cathepsin G were also inhibited by LPS from P. aeruginosa. LPS from P. aeruginosa was shown to be a competitive inhibitor of the enzyme activity of cathepsin G. Elastase enzyme activity was also inhibited noncompetitively by LPS, but the enzyme was not bactericidal. We have concluded that all three bactericidal proteins (BP 55, BP 30, and cathepsin G) may bind to the LPS of the outer membrane of P. aeruginosa. It appears that the enzyme active site must be available for cathepsin G to kill P. aeruginosa and that the active site may be involved in the binding of cathepsin G to P. aeruginosa.Polymorphonuclear leukocytes (PMNL) occupy a central role in host defense and destroy intracellular microorganisms by both oxygen-dependent and oxygen-independent mechanisms. As reviewed by Spitznagel (45) and Thomas et al. (47), several proteins are implicated in oxygen-independent killing of microorganisms. Prominent among the cationic bactericidal proteins thus far purified from human PMNL is a 58to 60-kDa bactericidal/permeability-increasing protein (B/PI) described by Weiss et al. (51). B/PT is bactericidal toward Salmonella typhimurium and Escherichia coli. Shafer et al. have described two cationic antibacterial proteins (CAP) of 57 kDa (CAP57) and 37 kDa (CAP37) that are bactericidal toward S. typhimurium (37). We have described a 55-kDa glycoprotein (BP 55) that was isolated from normal human PMNL and was bactericidal toward Pseudomonas aeruginosa (19,20). The smaller cationic defensins (3.5 to 4.0 kDa) kill a spectrum of microorganisms, including P. aeruginosa (10, 16).More recently, reports by Gabay et al. (9) and Campanelli et al. (6) of a 30-kDa protein, called azurocidin, which is bactericidal for E. coli and Streptococcus faecalis and fungicidal for Candida albicans, have generated a great deal of interest. These same investigators have recalled attention to the bactericidal activity of serine proteinase...

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confidence: 77%

Section: Discussionmentioning

confidence: 99%

Comparison of granule proteins from human polymorphonuclear leukocytes which are bactericidal toward Pseudomonas aeruginosa

1991

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“…The initial studies, which suggested a role for neutrophils, can be grouped into three sets of observations: i) both Skamene (72) and Czyprynski & Campbell and their associates (73) correlated resistance to Listeria with the mobilization of neutrophils and macrophages to infective foci; ii) the histological analysis of the 24-48 h after infection showed tnicroabscess. more particularly in the hepatocytes (74-77); indeed, the North laboratory correlated these with death of liver cells and with the control of tlie infection; and iii) Pixie Campbell herself called attention to the neutrophil as a listericidal cell, testing in culture assays (78,79).…”

Section: The Neutrophi! Response and The Liver Infectionmentioning

confidence: 99%

Studies in listeriosis show the strong symbiosis between the innate cellular system and the T‐cell response

Unanue¹

1997

Immunological Reviews

233

150

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Resistance to infection with Listeria monocytogenes involves a series of cellular interactions, many of which are carried out by cytokines. Macrophages, NK cells and neutrophils participate in early stages of Listeria resistance. The neutrophil is specially important for clearance of the liver phase of listeriosis. Macrophages and NK cells interact by way of IL-12 and TNF, which induce the NK cell to produce IFN-gamma. IFN-gamma is the major macrophage-activating cytokine. The CB-17 SCID mouse shows these cellular interactions restricting the growth of Listeria, without its elimination. CD4 and/or CD8 T cells bring about sterilizing immunity. Macrophages influence the lymphocyte response by way of antigen presentation and also by promoting Th 1 differentiation. Thus, elimination of Listeria requires a symbiosis between innate immunity and the T-cell system.

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“…infection of mice with intracellular pathogens like listeriae or mycobacteria induces rapid infiltration of high numbers of neutrophils, but the significance of this neutrophilia is not known (2-5, 44). In culture, the infiltrating neutrophils are capable of killing listeriae and release oxygen derivatives and enzymes with antilisterial activity (1,12,18; reviewed in reference 32). In our own studies, treatment of mice with monoclonal antibodies against IL-1 rendered them profoundly sensitive to listeriae (39).…”

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confidence: 99%

Neutrophils are involved in acute, nonspecific resistance to Listeria monocytogenes in mice

1993

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The importance of neutrophils in killing extracellular, pyogenic bacteria has long been established. However, there is only indirect evidence for a role for neutrophils in resistance against intracellular organisms. In this study, we directly demonstrate the involvement of neutrophils in defense against Listeria monocytogenes in normal C.B-17 immunocompetent and C.B-17 SCID mice. Because of the lack of sterilizing T-cell immunity, SCID mice are unable to completely eliminate listeriae systemically and become chronically infected. Both immunocompetent and SCID mice treated with a specific neutrophil-depleting monoclonal antibody during the early stages of Listeria infection were rendered remarkably sensitive to the organism, with a high level of mortality resulting from enhanced bacterial growth. At a late stage of infection in SCID mice, however, administration of neutrophil-depleting antibody did not affect mortality. In spite of the neutrophil depletion, other parameters of nonspecific immune function were normal. Macrophage infiltration to the site of infection and macrophage expression of major histocompatibility complex class II molecules were unaffected. Moreover, NK cell functions were normal as measured by infiltration to an infection site and gamma interferon production. These data demonstrate an important role for neutrophils in controlling the acute phase ofListeria infection, cooperating with, and yet independent of, macrophages and NK cells.

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Listericidal activity of human neutrophil cathepsin G

Cited by 19 publications

References 15 publications

Comparison of granule proteins from human polymorphonuclear leukocytes which are bactericidal toward Pseudomonas aeruginosa

Comparison of granule proteins from human polymorphonuclear leukocytes which are bactericidal toward Pseudomonas aeruginosa

Studies in listeriosis show the strong symbiosis between the innate cellular system and the T‐cell response

Neutrophils are involved in acute, nonspecific resistance to Listeria monocytogenes in mice

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