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Molecular cloning and characterization of three beta-defensins from canine testes.

Mammalian beta-defensins are small cationic peptides possessing broad antimicrobial and physiological activities. Because dogs are particularly resilient to sexually transmitted diseases, it has been proposed that their antimicrobial peptide repertoire might provide insight into novel antimicrobial therapeutics and treatment regimens. To investigate this proposal, we cloned the full-length cDNA of three canine beta-defensin isoforms (cBD-1, -2, and -3) from canine testicular tissues. Their predicted peptides share identical N-terminal 65-amino-acid residues, including the beta-defensin consensus six-cysteine motif. The two longer isoforms, cBD-2 and -3, possess 4 and 34 additional amino acids, respectively, at the C terminus. To evaluate the antimicrobial activity of cBD, a 34-amino-acid peptide derived from the shared mature peptide region was synthesized. Canine beta-defensin displayed broad antimicrobial activity against gram-positive bacteria (Listeria monocytogenes and Staphylococcus aureus; MICs of 6 and 100 mug/ml, respectively), gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, and Neisseria gonorrhoeae; MICs of 20 to 50, 20, and 50 mug/ml, respectively), and yeast (Candida albicans; MIC of 5 to 50 mug/ml) and lower activity against Ureaplasma urealyticum and U. canigenitalium (MIC of 200 mug/ml). Antimicrobial potency was significantly reduced at salt concentrations higher than 140 mM. All three canine beta-defensins were highly expressed in testis. In situ hybridization indicated that cBD-1 was expressed primarily in Sertoli cells within the seminiferous tubules. In contrast, cBD-2 was located primarily within Leydig cells. The longest isoform, cBD-3, was detected in Sertoli cells and to a lesser extent in the interstitium. The tissue-specific expression and broad antimicrobial activity suggest that canine beta-defensins play an important role in host defense and other physiological functions of the male reproductive system.

Amino Acid Sequence↗

Distinct defensin profiles in Neisseria gonorrhoeae and Chlamydia trachomatis urethritis reveal novel epithelial cell-neutrophil interactions.

Defensins are key participants in mucosal innate defense. The varied antimicrobial activity and differential distribution of defensins at mucosal sites indicate that peptide repertoires are tailored to site-specific innate defense requirements. Nonetheless, few studies have investigated changes in peptide profiles and function after in vivo pathogen challenge. Here, we determined defensin profiles in urethral secretions of healthy men and men with Chlamydia trachomatis- and Neisseria gonorrhoeae-mediated urethritis by immunoblotting for the epithelial defensins HBD1, HBD2, and HD5 and the neutrophil defensins HNP1 to -3 (HNP1-3). HBD1 was not detectable in secretions, and HBD2 was only induced in a small proportion of the urethritis patients; however, HD5 and HNP1-3 were increased in C. trachomatis infection and significantly elevated in N. gonorrhoeae infection. When HNP1-3 levels were low, HD5 appeared mostly as the propeptide; however, when HNP1-3 levels were >10 microg/ml, HD5 was proteolytically processed, suggesting neutrophil proteases might contribute to HD5 processing. HD5 and HNP1-3 were bactericidal against C. trachomatis and N. gonorrhoeae, but HD5 activity was dependent upon N-terminal processing of the peptide. In vitro proteolysis of proHD5 by neutrophil proteases and analysis of urethral secretions by surface-enhanced laser desorption ionization substantiated that neutrophils contribute the key convertases for proHD5 in the urethra during these infections. This contrasts with the small intestine, where Paneth cells secrete both proHD5 and its processing enzyme, trypsin. In conclusion, we describe a unique defensin expression repertoire in response to inflammatory sexually transmitted infections and a novel host defense mechanism wherein epithelial cells collaborate with neutrophils to establish an antimicrobial barrier during infection.

Chlamydia Infections↗

Human beta-defensins suppress human immunodeficiency virus infection: potential role in mucosal protection.

Beta-defensins are small (3 to 5 kDa in size) secreted antimicrobial and antiviral proteins that are components of innate immunity. Beta-defensins are secreted by epithelial cells, and they are expressed at high levels in several mucosae, including the mouth, where the concentration of these proteins can reach 100 microg/ml. Because of these properties, we wondered whether they could be part of the defenses that lower oral transmission of human immunodeficiency virus (HIV) compared to other mucosal sites. Our data show that select beta-defensins, especially human beta-defensin 2 (hBD2) and hBD3, inhibit R5 and X4 HIV infection in a dose-dependent manner at doses that are compatible with or below those measured in the oral cavity. We observed that beta-defensin treatment inhibited accumulation of early products of reverse transcription, as detected by PCR. We could not, however, detect any reproducible inhibition of env-mediated fusion, and we did not observe any modulation of HIV coreceptors following treatment with hBD1 and hBD2, in both resting and phytohemagglutinin-activated cells. Our data instead suggest that, besides a direct inactivation of HIV virions, hBD2 inhibits HIV replication in the intracellular environment. Therefore, we speculate that beta-defensins mediate a novel antiretroviral mechanism that contributes to prevention of oral HIV transmission in the oral cavity. Immunohistochemical data on hBD2 expression in oral mucosal tissue shows that hBD2 is constitutively expressed, forming a barrier layer across the epithelium in healthy subjects, while in HIV-positive subjects levels of hBD2 expression are dramatically diminished. This may predispose HIV-positive subjects to increased incidence of oral complications associated with HIV infection.

Cell Fusion↗

Roles of antimicrobial peptides such as defensins in innate and adaptive immunity.

A number of antimicrobial peptides such as defensins have multiple functions in host defence. Defensins are produced not only by phagocytic cells and lymphocytes, but also by the epithelial cell lining of the gastrointestinal and genitourinary tracts, the tracheobronchial tree, and keratinocytes. Some are produced constitutively, whereas others are induced by proinflammatory cytokines and exogenous microbial products. Defensins produced by cells in the course of innate host defence serve as signals which initiate, mobilise, and amplify adaptive immune host defences. Administration of defensins with antigens to mice enhances both cellular (Th1-dependent) and humoral (Th2-dependent) cytokine production and immune responses. Linkage of defensins to weak tumour antigens potentiates their immunoadjuvant effects. Defensins use multiple cellular receptors, which endows them with the capacity to marshall adaptive host defences against microbial invaders.

Animals↗

Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense.

Mammals generate a diverse array of antimicrobial proteins, largely represented by defensins or cathelicidins. The direct in vitro microbicidal activity of antimicrobial proteins has long been considered an important innate immune defense, although the in vivo relevance has only very recently been established for certain defensins and cathelicidins. Mammalian defensins and cathelicidins have also been shown to have multiple receptor-mediated effects on immune cells. Beta-defensins interact with CCR6; murine beta-defensin-2 in addition activates TLR4. Cathelicidins act on FPRL1-expressing cells. Furthermore, several defensins have considerable immunoenhancing activity. Thus, it appears that mammalian antimicrobial proteins contribute to both innate and adaptive antimicrobial immunity.

Animals↗

Defensins: antimicrobial and cytotoxic peptides of mammalian cells.

Defensins are antimicrobial and cytotoxic peptides that contain 29-35 amino acid residues, including six invariant cysteines whose intramolecular disulfide bonds cyclize and stabilize them in a complexly folded, triple-stranded beta-sheet configuration. Generated by the proteolytic processing of 93-95 amino acid precursor peptides, the constitute > 5% of the total cellular protein in human and rabbit neutrophils (polymorphonucleated neutrophils--PMN) and are also produced by rabbit lung macrophages and by mouse and rabbit small intestinal Paneth cells. Despite their prominence in rat PMN, defensins are not found in murine PMN. The antimicrobial spectrum of defensins includes gram positive and gram negative bacteria, mycobacteria, T. pallidum, many fungi, and some enveloped viruses. Defensins exert nonspecific cytotoxic activity against a wide range of normal and malignant targets, including cells resistant to TNF-alpha and NK-cytolytic factor. They appear to kill mammalian target cells and microorganisms by a common mechanism, which involves initial electrostatic interactions with negatively charged target cell surface molecules (likely the head groups of polar membrane lipids), followed by insertion into the cell membranes which they permeabilize, forming voltage-regulated channels. In addition to their antimicrobial and cytotoxic properties, some defensins act as opsonins, while others inhibit protein kinase C, bind specifically to the ACTH receptor and block steroidogenesis or act as selective chemoattractants for monocytes. Defensins are a newly delineated family of effector molecules whose contribution to host defense, inflammation, and cytotoxicity may be considerable for humans, even though it is unlikely to be revealed by experimentation with mice.

Amino Acid Sequence↗

Inhibition of pathologic retinal neovascularization by alpha-defensins.

Proliferative retinopathies, such as those complicating prematurity and diabetes, are major causes of blindness. A prominent feature of these retinopathies is excessive neovascularization, which is orchestrated by the hypoxia-induced vascular endothelial growth factor (VEGF) stimulating endothelial cells and the integrin-mediated adhesive interactions of endothelial cells with extracellular matrix components such as fibronectin (FN). Recently, we demonstrated that alpha-defensins interfere with alpha5beta1-FN interactions and dependent endothelial cell functions. Here, alpha-defensins were studied in hypoxia-induced proliferative retinopathy. In vitro, alpha-defensins specifically inhibited alpha5beta1-integrin-dependent migration of bovine retinal endothelial cells (BRECs) to FN, attenuated the VEGF-stimulated increase in endothelial permeability, and blocked BREC proliferation and capillary sprout formation in 3-dimensional fibrin-matrices. An up-regulation of beta1-integrin and FN was observed in the retinal vessels in the mouse model of hypoxia-induced retinal angiogenesis. Systemic and local administration of alpha-defensins reduced retinal neovascularization by 45% and 60%, respectively, and this effect was comparable to the inhibitory effect of alpha5beta1-blocking antibody. alpha-Defensins were detected in human diabetic retinas associated with normal retinal vessels but were absent from proliferative lesions. Together, these data show that alpha-defensins inhibit pathologic retinal neovascularization in vivo and may provide a clinically efficient strategy against proliferative retinopathies.

Animals↗

High level expression of human epithelial beta-defensins (hBD-1, 2 and 3) in papillomavirus induced lesions.

BACKGROUND: Epithelial defensins including human beta-defensins (hBDs) and alpha-defensins (HDs) are antimicrobial peptides that play important roles in the mucosal defense system. However, the role of defensins in papillomavirus induced epithelial lesions is unknown. RESULTS: Papilloma tissues were prospectively collected from 15 patients with recurrent respiratory papillomatosis (RRP) and analyzed for defensins and chemokine IL-8 expression by quantitative, reverse-transcriptase polymerase chain reaction (RT-PCR) assays. HBD-1, -2 and -3 mRNAs were detectable in papilloma samples from all RRP patients and the levels were higher than in normal oral mucosal tissues from healthy individuals. Immunohistochemical analysis showed that both hBD-1 and 2 were localized in the upper epithelial layers of papilloma tissues. Expression of hBD-2 and hBD-3 appeared to be correlated as indicated by scatter plot analysis (r = 0.837, p < 0.01) suggesting that they were co-inducible in papillomavirus induced lesions. Unlike hBDs, only low levels of HD5 and HD6 were detectable in papillomas and in oral mucosa. CONCLUSION: Human beta-defensins are upregulated in respiratory papillomas. This novel finding suggests that hBDs might contribute to innate and adaptive immune responses targeted against papillomavirus-induced epithelial lesions.

Adult↗

Enteric defensin expression in necrotizing enterocolitis.

Immaturity of local innate defenses has been suggested as a factor involved in the pathophysiology of necrotizing enterocolitis (NEC). The mRNA of enteric human defensins 5 (HD5) and 6 (HD6), antibiotic peptides expressed in Paneth cells of the small intestine, have significantly lower levels of expression in fetal life compared with the term newborn and adult. In the current study, intracellular HD5 was demonstrated by immunohistochemistry at 24 wk of gestation, but at low levels, consistent with findings at the mRNA level. These data suggest that the low level enteric defensin expression, characteristic of normal intestinal development, may contribute to the immaturity of local defense, which predisposes the premature infant to NEC. To test if levels of defensin expression are altered in NEC, specimens from six cases of patients with NEC and five control subjects (four patients with atresia and one with meconium ileus) were analyzed to determine HD5 and HD6 mRNA levels by in situ hybridization. Compared with the control group, the level of enteric defensin expression per Paneth cell assessed by image analysis was increased 3-fold in cases of NEC (p = 0.02, analysis of variance and covariance). In addition, the number of Paneth cells was increased 2-fold in the small intestinal crypts of NEC specimens compared with those of control subjects (p < 0.01, covariance analysis). In healthy tissue, peptide levels within Paneth cells paralleled mRNA levels through development. In tissue from infants with NEC, the steady state level of intracellular peptide was not increased in conjunction with the observed rise in defensin mRNA. A straightforward interpretation of this finding is that HD5 is actively secreted in this setting and the Paneth cells maintain a constant steady state level of intracellular peptide, but the possibility of translational regulation of peptide expression is also consistent with these data. The associations between NEC and enteric defensin expression reported here offer support for future studies to address the role of these endogenous host defense factors in the pathophysiology of this disease.

Adult↗

cDNA cloning, tissue distribution, and subcellular localization of horseshoe crab big defensin.

A full-length cDNA for horseshoe crab big defensin with a strong antimicrobial activity was obtained from a hemocyte cDNA library. The open reading frame of the cDNA coded for an NH2-terminal signal sequence followed by a propeptide and the mature big defensin. The propeptide is linked to the mature protein through an -Arg-X-Lys/Arg-Arg- motif, the processing site for Kex2-like proteases. Northern blot analysis revealed that big defensin is expressed in all the tissues tested, suggesting that big defensin plays an important role not only in hemocytes but also in other tissues for host defense. The subcellular localization, determined by immunocytochemistry at ultrastructural level, confirmed the previous findings obtained by biochemical analysis that big defensin locates in both small and large granules in hemocytes. Big defensin is the first example to demonstrate the existence of broad tissue distribution in horseshoe crab.

Amino Acid Sequence↗

Defensins--components of the innate immune system in plants.

Plant defensins are small (c.a. 5 kDa), basic, cysteine-rich proteins with antimicrobial activities. They are ubiquitous in plants and form part of the innate immunity arsenal. Plant defensins are encoded by small multigene families and are expressed in various plant tissues, but are best characterized in seeds. They are typically produced as preproteins, however, a small subset are produced as larger precursors with C-terminal prodomains. To date, the three-dimensional solution structures of seven seed- and two floral-derived defensins have been elucidated by (1)H-NMR spectroscopy. Despite limited amino acid sequence identities, these defensins have comparable global folds with features that are characteristic of the cysteine-stabilized alphabeta (CSalphabeta) motif. Interestingly, their structures are remarkably similar to those of insect defensins and scorpion toxins. Functionally, these proteins exhibit a diverse array of biological activities, although they all serve a common function as defenders of their hosts. This review describes the distribution, biosynthesis, structure, function and mode of action of plant defensins and reflects on their potential in agribiotechnological applications.

Amino Acid Sequence↗

Inactivation of human beta-defensins 2 and 3 by elastolytic cathepsins.

beta-Defensins are antimicrobial peptides that contribute to the innate immune responses of eukaryotes. At least three defensins, human beta-defensins 1, 2, and 3 (HBD-1, -2, and -3), are produced by epithelial cells lining the respiratory tract and are active toward Gram-positive (HBD-3) and Gram-negative (HBD-1, -2, and -3) bacteria. It has been postulated that the antimicrobial activity of defensins is compromised by changes in airway surface liquid composition in lungs of patients with cystic fibrosis (CF), therefore contributing to the bacterial colonization of the lung by Pseudomonas and other bacteria in CF. In this report we demonstrate that HBD-2 and HBD-3 are susceptible to degradation and inactivation by the cysteine proteases cathepsins B, L, and S. In addition, we show that all three cathepsins are present and active in CF bronchoalveolar lavage. Incubation of HBD-2 and -3 with CF bronchoalveolar lavage leads to their degradation, which can be completely (HBD-2) or partially (HBD-3) inhibited by a cathepsin inhibitor. These results suggest that beta-defensins are susceptible to degradation and inactivation by host proteases, which may be important in the regulation of beta-defensin activity. In chronic lung diseases associated with infection, overexpression of cathepsins may lead to increased degradation of HBD-2 and -3, thereby favoring bacterial infection and colonization.

Anti-Bacterial Agents↗

Alpha-defensins in the prevention of HIV transmission among breastfed infants.

Alpha-defensins have been observed to have anti-HIV activity but have not been investigated in relation to mother-to-child HIV transmission. We measured the concentration of alpha-defensins in breast milk of HIV-positive mothers and tested whether the concentrations were associated with HIV transmission. A nested case-control study of 32 HIV-positive women who transmitted HIV to their infants and 52 randomly selected HIV-positive women who did not transmit HIV to their infants was conducted in Lusaka, Zambia. alpha-Defensins were detected in most (79%) of the milk samples tested. Concentrations of alpha-defensins increased as breast milk HIV RNA quantity increased, and breast milk HIV RNA quantity was, in turn, a strong and significant predictor of HIV transmission. After adjustment for milk HIV RNA quantity, however, alpha-defensin concentration was significantly associated with a decreased risk of intrapartum and postnatal HIV transmission (odds ratio = 0.3, 95% confidence interval: 0.09-0.93). Our data suggest that there may be a role for alpha-defensins in prevention of HIV transmission to breastfed infants.

Adult↗

[Purification and antimicrobial activity of human neutrophil defensins].

Neutrophils are one of the weapons of host defenses against microbial infection. Their ability to kill the invading microorganisms depends on two principle mechanisms. One depends on production of reactive oxygen intermediates (ROI) by stimulated neutrophils, and the other depends on the delivery of antimicrobial contents of the neutrophils' cytoplasmic granules, oxygen-independent. The defensins have the highest concentration in the neutrophils, and the broadest antimicrobial spectrum, being capable of killing gram-positive and gram-negative bacteria, fungi and some envelope viruses. We purified human defensins from the neutrophils' granules by gel permeation chromatography and SDS-preparative acrylamide gel electrophoresis. The molecular weight of human defensins is between 3,000-4,000 daltons. After testing, C. neoformans was susceptible to these defensins. Under condition of 37 degrees C, pH 7.4 and low ionic strength, antifungal activity by human defensins was related to its concentration and incubating time. All of these illustrate that nonoxidative killing mechanism of neutrophils, especially the function of defensins is very important in host defenses.

Antifungal Agents↗

[Effect of recombinant beta-defensin-2 peptide on apoptosis of pulmonary tissue in rats with sepsis].

OBJECTIVE: To investigate the effect of recombinant beta-defensin 2 (BD-2) on the apoptosis of pulmonary tissue in rats with sepsis. METHODS: Forty-eight SD rats were randomly divided into defensin group and controls. In control group 24 rats received 10(7)PFU adenovirus via trachea intubation. In defensin group 24 rats received 10(7)PFU recombinant adenovirus carrying all expression cassette of rat BD-2 (Ad-rBD2). All rats received cecal ligation and puncture (CLP) to induce sepsis 48 h following the administration of adenovirus. Rats of both groups were sacrificed at 0, 12, 36 and 72 h after CLP; lungs were removed and fixed for Haematoxylin and Eosin (HE) stain. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) technique. RESULT: The apoptosis index (AI) of lung cells increased significantly following CLP in control group,while it was significantly lower in defensin group than that of control group (P<0.05). In addition, a significant alveolar damage, interstitial edema, and infiltration of inflammatory cells were observed in control lungs, while it was less severe in defensin group. CONCLUSION: Recombinant beta-defensin 2 may reduce the apoptosis of lung cells and attenuate lung injury.

Adenoviridae↗

Defensin-rich dense granules of human neutrophils.

Defensins are a newly recognized class of small, cationic polypeptides that have in vitro microbicidal activity toward certain bacteria, fungi, and viruses. Human neutrophil granules were separated into 13 density fractions by using a high-resolution Percoll gradient centrifugation procedure, and the distribution of the three defensin polypeptides in these fractions was determined. Levels of defensins and several granule marker proteins were estimated in each fraction from relative staining intensities of bands following acid-urea and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of total acid-extractable proteins. These results were confirmed by enzyme immunoassay measurements of defensins and quantitative determinations of the typical azurophil granule components, myeloperoxidase, beta-glucuronidase, lysozyme, and elastase. The five higher density granule fractions (H1 through H5) contained fourfold higher relative amounts of defensins as compared with the eight lower density fractions (L1 through L8), accounting for approximately 50% of the total protein. In particular, fraction H5 was especially enriched in defensins but was relatively deficient in myeloperoxidase, beta-glucuronidase, lysozyme, and elastase. Ultrastructural morphology showed that fraction H5 contained the largest granules. Seventy percent of these granules exhibited electron-dense rims and electron-lucent central regions when stained with methanolic uranyl acetate-lead citrate, and 70% showed this same characteristic rim-staining pattern after limited reaction (30 minutes) for peroxidase with diaminobenzidine. These distinctively large, rim-stained granules were identified in intact, mature peripheral blood neutrophils as well as in human bone marrow promyelocytes, indicating that their synthesis occurs during early myeloid development. This unusual granule type may play a specialized role in the microbicidal functions of the neutrophil, distinct from that of typical azurophil granules.

Blood Proteins↗

Distinct temporal patterns of defensin mRNA regulation during drug-induced differentiation of human myeloid leukemia cells.

Defensins are microbicidal peptides and the principal constituents of neutrophil primary granules. They are presumed to play a prominent role in innate host defenses. We examined defensin mRNA levels during drug-induced differentiation of the promyelocytic leukemia cell line, HL-60. Transcription was restricted to promyelocyte, myelocyte, and very early metamyelocyte stages of the granulocytic pathway. Complete downregulation occurred during late granulocytic maturation or early during phorbol ester-promoted differentiation along the monocyte/macrophage lineage. Retinoic acid (RA) was the strongest inducer of defensin mRNA accumulation, even at doses too low to effect morphologic changes; the initial (first 48 hours), gradual increase resulted from transcriptional activation and was enhanced by granulocyte colony-stimulating factor. In contrast, addition of hybrid polar compounds led to a transient, drug-specific downregulation within the same time period, apparently by means of selectively induced, biphasic degradation of transcripts. Subsequent increase in transcript levels was faster and more pronounced with hexamethylene bisacetamide, relative to dimethyl sulfoxide (DMSO). DMSO-promoted effects were strikingly different in serum-free medium or in the presence of the tyrosine kinase inhibitor, genistein. Under these conditions, and although differentiation was unaffected, early defensin mRNA downregulation was final. The effect did not occur with RA and expression of other myeloid-specific genes was also unchanged. Addition of selected cytokines caused a similar "dip," only at earlier times and uncoupled from differentiation. Tumor necrosis factor-alpha markedly induced defensin levels after 2 days in previously untreated HL-60 cells, but inhibited expression in RA-differentiated cells. These results begin to detail a complex regulation of defensin mRNA synthesis with both spatial and temporal control elements, and a unique modulation by chemical agents, cytokines, and serum-factors.

Acetamides↗

Neutrophil activation in preeclampsia. Are defensins and lactoferrin elevated in preeclamptic patients?

OBJECTIVE: To determine if human defensins and lactoferrin, both markers of neutrophil activation, are elevated in preeclamptic plasma. STUDY DESIGN: Blood samples were obtained from 18 preeclamptic and 29 normal pregnant women in the third trimester. Demographic and clinical data were obtained from the medical record. No patient had evidence of labor and/or infection when blood was drawn. Preeclamptic patients were defined by elevated blood pressure, 140/90 mm Hg, proteinuria of > 300 mg in a 24-hour collection and hyperuricemia. Human defensins and lactoferrin were measured by enzyme immunoassay of plasma samples diluted 1:100 and 1:10, respectively. Standard curve values ranged from 0.25 to 16 ng/mL. Data for human defensins and lactoferrin are presented as median values +/-SE. Statistical analysis included Student's t test for comparison of clinical data, Mann-Whitney U test for comparison of absolute values between groups and Fisher's exact test, when appropriate. RESULTS: There was no difference in age or estimated gestational age between the two groups. There were more nulliparous patients in the preeclamptic group. Human defensin levels were significantly elevated (P = .005) in plasma of preeclamptic patients (25.1 ng/mL +/- 16.2) as compared to normal controls (9.0 ng/mL +/- 8.9). Nine of 18 (50%) preeclamptic patients and 2 of 29 (7%) normal controls had defensin levels above the low point on the standard curve (P = .001). There was no difference in lactoferrin levels between the two groups. CONCLUSION: Our results suggest that preeclampsia is associated with neutrophil activation. The biologic effect of elevated human defensins in preeclamptic plasma remains to be determined.

Adult↗