Antimicrobial peptide LL-37 and recombinant human mannose-binding lectin express distinct age- and pathogen-specific antimicrobial activity in human newborn cord blood .
There is a need to prevent and treat infection in newborns. One approach is administration of antimicrobial proteins and peptides (APPs) such as LL-37, a membrane-active cathelicidin antimicrobial peptide, and mannose-binding lectin (MBL), a pattern-recognition protein that binds to microbial surface polysaccharides resulting in opsonization and complement activation. Low plasma/serum levels of LL-37 and of MBL have been correlated with infection and exogenous administration of these agents may enhance host defense. The antimicrobial activity of LL-37 (15 µg/ml) or rMBL (0.5, 2 and 10 µg/ml) was tested in hirudin-anticoagulated preterm and term human cord blood (N = 12-14) against (SA) USA 300 (2x10 CFU/ml), (SE) 1457 (2x10 CFU/ml) and (CA) SC5314 (1x10 CFU/ml). After incubation (1, 45, or 180 min), CFUs were enumerated by plating blood onto agar plates. Supernatants were collected for measurement of MBL via ELISA. Preterm cord blood demonstrated impaired endogenous killing capacity against SA and SE compared to term blood. Addition of LL-37 strongly enhanced antimicrobial/antifungal activity vs SA, SE and CA in term blood and SE and CA in preterm blood. By contrast, rMBL showed modest fungistatic activity vs CA in a sub-analysis of term newborns with high basal MBL levels. Baseline MBL levels varied within preterm and term cohorts with no correlation to gestational age. In summary, exogenous LL-37 demonstrated significant antimicrobial activity against SA, SE and CA in term and SE and CA in preterm human blood tested . rMBL demonstrated modest antifungal activity in term cord blood of individuals with high baseline MBL levels. To the extent that our results predict the effects of APPs , development of APPs for prevention and treatment of infection should take into account host age as well as the target pathogen.
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R01 AI100135 / AI / NIAID NIH HHS / United States
R01 AI067353 / AI / NIAID NIH HHS / United States
U01 AI124284 / AI / NIAID NIH HHS / United States
U19 AI118608 / AI / NIAID NIH HHS / United States