We purified a molecule from the murine small intestine that killed both Escherichia coli and Listeria monocytogenes, and identified it as intestinal phospholipase A2 (iPLA2) by NH2-terminal sequencing and enzymatic measurements. The ability of iPLA2 to kill. L. monocytogenes was greatly enhanced by 5 mM calcium, inhibited by EGTA and abolished after reduction and alkylation, suggesting that enzymatic activity was required for iPLA2-mediated bactericidal activity. A mouse-avirulent phoP mutant, S. typhimurium 7953S, was 3.5-fold more susceptible to iPLA2 than its isogenic virulent parent, S. typhimurium 14028S (estimated minimal bactericidal concentrations 12.7 +/- 0.5 micrograms/ml vs. 43.9 +/- 4.5 micrograms/ml P < 0.001). Overall, these findings identify iPLA2 as part of the antimicrobial arsenal that equips Paneth cells to protect the small intestinal crypts from microbial invasion. Because iPLA2 is identical to Type 2 phospholipase A2 molecules found in other sites, including spleen, platelets and inflammatory exudate cells, this enzyme may also contribute to antibacterial defenses elsewhere in the body.
S S Harwig, L Tan, X D Qu, Y Cho, P B Eisenhauer, R I Lehrer
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Route and Type of Nutrition and Surgical Stress Influence Secretory Phospholipase A2 Secretion of the Murine Small Intestine
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Mucosal Immunology
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Neonatal antibiotic treatment alters gastrointestinal tract developmental gene expression and intestinal barrier transcriptome
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Physiological genomics | 2005 |
Bacterial Translocation
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Bactericidal and Antiendotoxic Properties of Short Cationic Peptides Derived from a Snake Venom Lys49 Phospholipase A 2
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Antimicrobial agents and chemotherapy | 2005 |
Defensins and Other Antimicrobial Peptides and Proteins
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Innate Immunity of the Gut: Mucosal Defense in Health and Disease
Q Yuan, WA Walker |
Journal of Pediatric Gastroenterology and Nutrition | 2004 |
Antimicrobial proteins and peptides: anti-infective molecules of mammalian leukocytes
O Levy |
Journal of leukocyte biology | 2004 |
The Innate Immune Response to Infection
SH Kaufmann, R Medzhitov, S Gordon |
2004 | |
Group IIA phospholipase A2 content of tears in patients with atopic blepharoconjunctivitis
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Graefe's Archive for Clinical and Experimental Ophthalmology | 2004 |
α-Defensins in the gastrointestinal tract
RN Cunliffe |
Molecular Immunology | 2003 |
Antimicrobial peptides in the first line defence of human colon mucosa
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Journal of Cataract & Refractive Surgery | 2003 |
Expression and regulation of antimicrobial peptides in the gastrointestinal tract
RN Cunliffe, YR Mahida |
Journal of leukocyte biology | 2003 |
Enteric Salmonella Infection Inhibits Paneth Cell Antimicrobial Peptide Expression
NH Salzman, MM Chou, H de Jong, L Liu, EM Porter, Y Paterson |
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Bactericidal properties of group IIa secreted phospholipase A2 against Pseudomonas aeruginosa clinical isolates
A Dubouix, C Campanac, J Fauvel, MF Simon, JP Salles, C Roques, H Chap, N Marty |
Journal of Medical Microbiology | 2003 |
Effect of Tryptophan Insertions on the Properties of the Human Group IIA Phospholipase A 2 : Mutagenesis Produces an Enzyme with Characteristics Similar to Those of the Human Group V Phospholipase A 2
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Biochemistry | 2003 |
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G Canny, O Levy, GT Furuta, S Narravula-Alipati, RB Sisson, CN Serhan, SP Colgan |
Proceedings of the National Academy of Sciences | 2002 |
Platelet-activating factor and lyso-PAF possess direct antimicrobial properties in vitro
HC Steel, R Cockeran, R Anderson |
APMIS | 2002 |
Expression of antimicrobial neutrophil defensins in epithelial cells of active inflammatory bowel disease mucosa
RN Cunliffe, M Kamal, FR Rose, PD James, YR Mahida |
Journal of clinical pathology | 2002 |
Phospholipase A2 enzymes
I Kudo, M Murakami |
Prostaglandins & Other Lipid Mediators | 2002 |
Lipid, lipase and lipocalin differences between tolerant and intolerant contact lens wearers
MJ Glasson, F Stapleton, MD Willcox |
Current Eye Research | 2002 |
Paneth cell trypsin is the processing enzyme for human defensin-5
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Nature Immunology | 2002 |
Invasion of Salmonella into human intestinal epithelial cells is modulated by HLA‐B27
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Rheumatology (Oxford, England) | 2002 |
Mucosal T cells regulate Paneth and intermediate cell numbers in the small intestine of T. spiralis-infected mice
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Clinical & Experimental Immunology | 2001 |
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Journal of Gastroenterology and Hepatology | 2001 |
Human defensin 5 is stored in precursor form in normal Paneth cells and is expressed by some villous epithelial cells and by metaplastic Paneth cells in the colon in inflammatory bowel disease
RN Cunliffe, FR Rose, J Keyte, L Abberley, WC Chan, YR Mahida |
Gut | 2001 |
Peptide Antibiotics: Discovery Modes Of Action And Applications
D Andreu, L Rivas |
Peptide Antibiotics: Discovery Modes Of Action And Applications | 2001 |
The Antibacterial Properties of Secreted Phospholipases A 2: A MAJOR PHYSIOLOGICAL ROLE FOR THE GROUP IIA ENZYME THAT DEPENDS ON THE VERY HIGH pI OF THE ENZYME TO ALLOW PENETRATION OF THE BACTERIAL CELL WALL
SA Beers, AG Buckland, RS Koduri, W Cho, MH Gelb, DC Wilton |
The Journal of biological chemistry | 2001 |
Bactericidal Properties of Human and Murine Groups I, II, V, X, and XII Secreted Phospholipases A 2
RS Koduri, JO Grönroos, VJ Laine, CL Calvez, G Lambeau, TJ Nevalainen, MH Gelb |
The Journal of biological chemistry | 2001 |
Role of gut flora on intestinal group II phospholipase A 2 activity and intestinal injury in shock
RA Rozenfeld, X Liu, I Deplaen, W Hsueh |
AJP Gastrointestinal and Liver Physiology | 2001 |
Immunological Aspects of Gastroenterology
YR Mahida |
2001 | |
Bactericidal Properties of Group IIA and Group V Phospholipases A 2
JO Grönroos, VJ Laine, MJ Janssen, MR Egmond, TJ Nevalainen |
Journal of immunology (Baltimore, Md. : 1950) | 2001 |
Helicobacter infection and phospholipase A2 enzymes: effect of Helicobacter felis-infection on the expression and activity of sPLA2 enzymes in mouse stomach
A Ottlecz, J J Romero, L M Lichtenberger |
Molecular and Cellular Biochemistry | 2001 |
Neutrophils: Molecules, Functions and Pathophysiological Aspects
V Witko-Sarsat, P Rieu, B Descamps-Latscha, P Lesavre, L Halbwachs-Mecarelli |
Laboratory Investigation | 2000 |
Gastric Metaplasia: A Frequently Overlooked Feature of Duodenal Biopsy Specimens in Untreated Celiac Disease
R Shaoul, MA Marcon, Y Okada, E Cutz, G Forstner |
Journal of Pediatric Gastroenterology and Nutrition | 2000 |
The significance of enzymic and other biological activities of proteins in relation to their capacity to serve as allergens
Shakib, Furmonaviciene |
Clinical & Experimental Allergy | 2000 |
Phospholipase A2 sécrétée de type IIA et syndrome inflammatoire
O Fourcade, MF Simon, FL Balle, J Fauvel, M Génestal, B Cathala, H Chap |
Réanimation Urgences | 2000 |
An 18.5 kDa protein from the amebocyte of Limulus polyphemus, homologous to the previously described amebocyte aggregation factor, expresses alternative phospholipase A2 activity
JC MacPherson, RS Jacobs |
Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology | 2000 |
Distribution of Group II Phospholipase A2 Protein and mRNA in Rat Tissues
KM Nyman, P Ojala, VJ Laine, TJ Nevalainen |
Journal of Histochemistry & Cytochemistry | 2000 |
The antibacterial properties of secreted phospholipases A2
AG Buckland, DC Wilton |
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | 2000 |
Increasing molecular diversity of secreted phospholipases A2 and their receptors and binding proteins
E Valentin, G Lambeau |
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | 2000 |
Bacterial cell membrane hydrolysis by secreted phospholipases A2: a major physiological role of human group IIa sPLA2 involving both bacterial cell wall penetration and interfacial catalysis
AG Buckland, EL Heeley, DC Wilton |
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | 2000 |
Anionic phospholipids, interfacial binding and the regulation of cell functions
AG Buckland, DC Wilton |
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | 2000 |
The Mom1AKR intestinal tumor resistance region consists of Pla2g2a and a locus distal to D4Mit64
RT Cormier, A Bilger, AJ Lillich, RB Halberg, KH Hong, KA Gould, N Borenstein, ES Lander, WF Dove |
Oncogene | 2000 |
Blockade of CD14 Increases Shigella- Mediated Invasion and Tissue Destruction
C Wennerås, P Ave, M Huerre, J Arondel, RJ Ulevitch, JC Mathison, P Sansonetti |
Journal of immunology (Baltimore, Md. : 1950) | 2000 |
Rac1 mutations produce aberrant epithelial differentiation in the developing and adult mouse small intestine
TS Stappenbeck, JI Gordon |
Development (Cambridge, England) | 2000 |
Cell-wall determinants of the bactericidal action of group IIA phospholipase A2 against Gram-positive bacteria
AK Foreman-Wykert, Y Weinrauch, P Elsbach, J Weiss |
Journal of Clinical Investigation | 1999 |
Modulation of acute and chronic inflammatory processes by cacospongionolide B, a novel inhibitor of human synovial phospholipase A2
PG Pastor, SD Rosa, AD Giulio, M Payá, MJ Alcaraz |
British Journal of Pharmacology | 1999 |
Gastrointestinal flora and its alterations in critical illness
JC Marshall |
Current Opinion in Clinical Nutrition and Metabolic Care | 1999 |
Gene expression of group II phospholipase A2 in intestine in Crohn's disease
MM Haapamaki, JM Gronroos, H Nurmi, K Alanen, TJ Nevalainen |
The American Journal of Gastroenterology | 1999 |
New developments in phospholipase A2
B Chaminade, F Balle, O Fourcade, M Nauze, C Delagebeaudeuf, A Gassama-Diagne, MF Simon, J Fauvel, H Chap |
Lipids | 1999 |
Phospholipases A2in Gastric Juice ofHelicobacter pylori– Positive and Negative Individuals
HT Huhtinen, JM Grönroos, MM Haapamäki, TJ Nevalainen |
Clinical Chemistry and Laboratory Medicine | 1999 |
Defensins and innate host defence of the gastrointestinal tract
CL Bevins, E Martin-Porter, T Ganz |
Gut | 1999 |
Phospholipase A2 in serum and colonic mucosa in ulcerative colitis
MM Nurm |
Scandinavian Journal of Clinical & Laboratory Investigation | 1999 |
THE GUT'S ROLE IN METABOLISM, MUCOSAL BARRIER FUNCTION, AND GUT IMMUNOLOGY
RC DeWitt, KA Kudsk |
Infectious Disease Clinics of North America | 1999 |
Advances in Cellular and Molecular Biology of Membranes and Organelles
MA Horwitz, DL Clemens |
Advances in Cellular and Molecular Biology of Membranes and Organelles | 1999 |
Both Group IB and Group IIA Secreted Phospholipases A 2 Are Natural Ligands of the Mouse 180-kDa M-type Receptor
L Cupillard, R Mulherkar, N Gomez, S Kadam, E Valentin, M Lazdunski, G Lambeau |
The Journal of biological chemistry | 1999 |
Innate mechanisms of epithelial host defense: spotlight on intestine
G Hecht |
American journal of physiology. Cell physiology | 1999 |
On the Diversity of Secreted Phospholipases A 2: CLONING, TISSUE DISTRIBUTION, AND FUNCTIONAL EXPRESSION OF TWO NOVEL MOUSE GROUP II ENZYMES
E Valentin, F Ghomashchi, MH Gelb, M Lazdunski, G Lambeau |
The Journal of biological chemistry | 1999 |
Cloning and Recombinant Expression of a Novel Mouse-secreted Phospholipase A 2
E Valentin, RS Koduri, JC Scimeca, G Carle, MH Gelb, M Lazdunski, G Lambeau |
The Journal of biological chemistry | 1999 |
Characterization of Metastatic Intestinal Adenocarcinoma with Differentiation into Multiple Morphologic Cell Types in a Virginia Opossum
MR Prater, RB Duncan, J Gaydos |
Veterinary pathology | 1999 |
Innate Antimicrobial Activity of Nasal Secretions
JR McGhee, AM Cole, P Dewan, T Ganz |
Infection and immunity | 1999 |
Innate Antimicrobial Activity of Nasal Secretions
JR McGhee, AM Cole, P Dewan, T Ganz |
Infection and immunity | 1999 |
Antibacterial Action of Extracellular Mammalian Group IIA Phospholipase A2 against Grossly ClumpedStaphylococcus aureus
VA Fischetti, ME Dominiecki, J Weiss |
Infection and immunity | 1999 |
Innate Antimicrobial Activity of Nasal Secretions
JR McGhee, AM Cole, P Dewan, T Ganz |
Infection and immunity | 1999 |
Induction of a Rat Enteric Defensin Gene by Hemorrhagic Shock
SH Kaufmann, MR Condon, A Viera, M DAlessio, G Diamond |
Infection and immunity | 1999 |
Survival, Physiology, and Lysis of Lactococcus lactis in the Digestive Tract
S Drouault, G Corthier, SD Ehrlich, P Renault |
Applied and environmental microbiology | 1999 |
New developments in phospholipase A2
B Chaminade, FL Balle, O Fourcade, M Nauze, C Delagebeaudeuf, A Gassama-Diagne, MF Simon, J Fauvel, H Chap |
Lipids | 1999 |
Group II phospholipase A2 in human male reproductive organs and genital tumors
M Kallajoki, KA Alanen, M Nevalainen, TJ Nevalainen |
The Prostate | 1998 |
Elevated Group 11 Phospholipase A2Mass Concentration in Serum and Colonic Mucosa in Crohn's Disease
MM Haapamäki, JM Grönroos, H Nurmi, K Söderlund, H Peuravuori, K Alanen, TJ Nevalainen |
Clinical Chemistry and Laboratory Medicine | 1998 |
Expression of group II phospholipase A2 in Paneth cells of an adenoma of the rectum
TJ Nevalainen, TJ Haapanen, P Rajala, T Ekfors |
APMIS | 1998 |
Potential role of epithelial cell-derived histone H1 proteins in innate antimicrobial defense in the human gastrointestinal tract
FR Rose, K Bailey, JW Keyte, WC Chan, D Greenwood, YR Mahida |
Infection and immunity | 1998 |
Regulation of secretory type-II phospholipase A2 and of lysophosphatidic acid synthesis
O Fourcade, FÇ Balle, J Fauvel, MF Simon, H Chap |
Advances in Enzyme Regulation | 1998 |
Analysis of the Mom1 Modifier of Intestinal Neoplasia in Mice
KA Gould, WF Dove |
Experimental Lung Research | 1998 |
Identification of Functional Domains of Rat Intestinal Phospholipase B/Lipase: ITS cDNA CLONING, EXPRESSION, AND TISSUE DISTRIBUTION
H Takemori, FN Zolotaryov, L Ting, T Urbain, T Komatsubara, O Hatano, M Okamoto, H Tojo |
The Journal of biological chemistry | 1998 |
Secretory Phospholipase A 2 Is the Principal Bactericide for Staphylococci and Other Gram-Positive Bacteria in Human Tears
XD Qu, RI Lehrer |
Infection and immunity | 1998 |
Cloning of intestinal phospholipase A2 from intestinal epithelial RNA by differential display PCR
S Keshav, AJ McKnight, R Arora, S Gordon |
Cell Proliferation | 1997 |
Secretory phospholipase Pla2g2a confers resistance to intestinal tumorigenesis
RT Cormier, KH Hong, RB Halberg, TL Hawkins, P Richardson, R Mulherkar, WF Dove, ES Lander |
Nature Genetics | 1997 |
Group II Phospholipase A2in Nasal Fluid, Mucosa and Paranasal Sinuses
HJ Aho, R Grénman, J Sipila, H Peuravuori, J Hartikainen, TJ Nevalainen |
Acta Oto-laryngologica | 1997 |
Lipid metabolism and APC: implications for colorectal cancer prevention
AJ Watson, RN DuBois |
The Lancet | 1997 |
Localization of human intestinal defensin 5 in Paneth cell granules
EM Porter, L Liu, A Oren, PA Anton, T Ganz |
Infection and immunity | 1997 |
Expression of Human Group II Phospholipase A 2 in Transgenic Mice
TJ Nevalainen, VJ Laine, DS Grass |
Journal of Histochemistry & Cytochemistry | 1997 |
Examining the Role of Paneth Cells in the Small Intestine by Lineage Ablation in Transgenic Mice
EM Garabedian, LJ Roberts, MS McNevin, JI Gordon |
The Journal of biological chemistry | 1997 |
Eicosanoids and other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury 3
KV Honn, LJ Marnett, S Nigam, RL Jones, PY Wong |
1997 | |
Broad-spectrum antimicrobial activity of human intestinal defensin 5
EM Porter, E van Dam, EV Valore, T Ganz |
Infection and immunity | 1997 |
The potent anti-Staphylococcus aureus activity of a sterile rabbit inflammatory fluid is due to a 14-kD phospholipase A2
Y Weinrauch, P Elsbach, LM Madsen, A Foreman, J Weiss |
Journal of Clinical Investigation | 1996 |
Antibiotic proteins of polymorphonuclear leukocytes
O Levy |
European Journal of Haematology | 1996 |
Reversible inhibition by protamine of human synovial and rabbit platelet secretory phospholipase A2
S Emadi |
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism | 1996 |
Potent Bactericidal Activity Towards Gram-Positive Bacteria of Mammalian Group II Phospholipase A2 Mobilized in Inflammatory Fluids
LM Madsen, Y Weinrauch, J Weiss |
Annals of the New York Academy of Sciences | 1996 |
Inhibition of the activity of pro-inflammatory secretory phospholipase A(2) by acute phase proteins
W Pruzanski, E Stefanski, P Vadas |
Mediators of Inflammation | 1996 |
Genetic evaluation of candidate genes for the Mom1 modifier of intestinal neoplasia in mice
KA Gould, C Luongo, AR Moser, MK McNeley, N Borenstein, A Shedlovsky, WF Dove, K Hong, WF Dietrich, ES Lander |
Genetics | 1996 |
Transgenic model for the discovery of novel human secretory non-pancreatic phospholipase A2 inhibitors
N Fox, M Song, J Schrementi, JD Sharp, DL White, DW Snyder, LW Hartley, DG Carlson, NJ Bach, RD Dillard, SE Draheim, JL Bobbitt, L Fisher, ED Mihelich |
European Journal of Pharmacology | 1996 |
Determinants of activation by complement of group II phospholipase A2 acting against Escherichia coli
L M Madsen, M Inada, J Weiss |
Infection and immunity | 1996 |
Novel Group V Phospholipase A 2 Involved in Arachidonic Acid Mobilization in Murine P388D 1 Macrophages
MA Balboa, J Balsinde, MV Winstead, JA Tischfield, EA Dennis |
The Journal of biological chemistry | 1996 |
Human Enteric Defensins: GENE STRUCTURE AND DEVELOPMENTAL EXPRESSION
EB Mallow, A Harris, N Salzman, JP Russell, RJ DeBerardinis, E Ruchelli, CL Bevins |
The Journal of biological chemistry | 1996 |
Secretion of type II phospholipase A2 and cryptdin by rat small intestinal Paneth cells
XD Qu, KC Lloyd, JH Walsh, RI Lehrer |
Infection and immunity | 1996 |
Inhibition of phospholipase A2 activities and some inflammatory responses by the marine product ircinin
R Cholbi, ML Ferrdndiz, MC Terencio, MJ Alcaraz, M Payd, SD Rosa |
Naunyn-Schmiedeberg's Archives of Pharmacology | 1996 |
Determinants of activation by complement of group II phospholipase A2 acting against Escherichia coli.
Madsen LM, Inada M, Weiss J |
Infection and immunity | 1996 |
The secretory phospholipase A2 gene is a candidate for the Mom1 locus, a major modifier of ApcMin-induced intestinal neoplasia
M MacPhee, KP Chepenik, RA Liddell, KK Nelson, LD Siracusa, AM Buchberg |
Cell | 1995 |
A Natural Disruption of the Secretory Group II Phospholipase A 2 Gene in Inbred Mouse Strains
BP Kennedy, P Payette, J Mudgett, P Vadas, W Pruzanski, M Kwan, C Tang, DE Rancourt, WA Cromlish |
The Journal of biological chemistry | 1995 |