hBD-2 peptide – Antimicrobial peptide and Kv1.3 channel blocker
Human beta-defensin-2(hBD-2) peptide,also known as skin-antimicrobial peptide 1 (SAP1) is a cysteine-rich cationic antimicrobial peptide of 41 amino acids. It was originally isolated from skin cells of psoriasis patients. hBD-2 peptide,which belongs to the defensin family,is implicated in the innate immunity thanks to its antimicrobial activity. Thus,β-defensins can play a role at the cutaneous level by limiting the use of antibiotics in severe burns and disease like psoriasis. Moreover,at the pulmonary level,defensins might be involved in the resorption of the infection in cases of cystic fibrosis. hBD-2 peptide is produced after stimulation of epithelial cells following their contact with some organisms like Gram-negative bacteria and Candida Albicans,fungus or cytokines such as TNF-alpha and IL-1 beta. This antimicrobial activity was shown to be microbicidal at concentrations greater than 1 µM and was lethal for E.Coli and pseudomonas (LD90 : 10 mg/mL) and Candida Albicans (LD90 : 25 mg/mL). Besides its antimicrobial activity , hBD-2 also exhibits proinflammatory properties as chemoattractants for memory T-cells,immature dendritic cells,mast cells and neutrophils. hBD-2 peptide has also demonstrated inhibitory activity of the voltage-gated potassium channel Kv1.3 at picomolar concentration. Kv1.3 are overexpressed by T-cells in case of autoimmune disorders
Objective:Human beta-defensin-2 (HBD-2) is a potent antimicrobial peptide that is part of the innate immune response. The purpose of this study was to determine whether HBD-2 is present in amniotic fluid and if its concentration changes with microbial invasion of the amniotic cavity (MIAC) and labor.
Study design:Amniotic fluid was retrieved by amniocentesis from 318 patients in the following groups: (1) mid-trimester (n=75); (2) term not in labor (n=28) and in labor (n=51); (3) preterm labor and intact membranes without MIAC who delivered at term (n=36),who delivered preterm without MIAC (n=52),and preterm labor with MIAC who delivered preterm (n=25); and (4) preterm premature rupture of membranes (preterm PROM) with (n=25) and without MIAC (n=26). MIAC was defined as a positive amniotic fluid culture for microorganisms. Amniotic fluid HBD-2 concentrations were determined using a sensitive and specific ELISA. Non-parametric statistics were used for analysis.
Results:(1) HBD-2 was detected in all amniotic fluid samples; (2) the concentration of HBD-2 did not change with gestational age from mid-trimester to term (p=0.8); (3) intra-amniotic infection was associated with a significant increase in amniotic fluid concentrations of HBD-2 in both women with preterm labor and intact membranes,and women with preterm PROM (p<0.05 for each comparison); (4) patients with preterm labor and a negative amniotic fluid culture who delivered preterm had a higher median amniotic fluid HBD-2 concentration than those with preterm labor who delivered at term (p=0.001); and (5) among patients with preterm labor without MIAC,those who had intra-amniotic inflammation (amniotic fluid white blood cell count>100 cells per mL) had a higher median amniotic fluid concentration of HBD-2 than those without this condition (p<0.002).
Conclusion:(1) Amniotic fluid contains HBD-2,a natural antimicrobial peptide,and this may account for some of the antimicrobial activity of amniotic fluid; (2) amniotic fluid HBD-2 concentrations are increased in women with MIAC,regardless of the membrane status (intact membranes or PROM); and (3) we propose that amniotic fluid HBD-2 is part of the innate immune system within the amniotic cavity.
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