Type III GBS is a leading cause of neonatal sepsis and meningitis. Recruitment of PMN to the site of infection is a critical step in host defense and may be aided by local release of chemotactic factors such as LTB4. GM-CSF, a cytokine produced by T lymphocytes, endothelial cells and macrophages, promotes granulopoiesis and enhances PMN functions such as phagocytosis and superoxide production. In animal models of GBS sepsis, the administration of GM-CSF alone or GM-CSF plus antibiotics significantly decreases mortality when compared to controls. Previously we have shown that N-PMN release LTB4 in response to opsonized III GBS. We investigated the effect of GM-CSF on LTB4 release by N-PMN stimulated with III-GBS. N-PMN were isolated from cord blood of healthy term infants after uncomplicated delivery via C-section. N-PMN (6×106mL) were exposed to GM-CSF (0.03-10 ng/mL) for 15 min and stimulated with III-GBS(108 cfu/mL). III GBS was opsonized with type-specific IgG antibody(2.5 μg/mL). LTB4 was measured by RIA. GM-CSF augmented III GBS-induced LTB4 production by N-PMN in a dose dependent manner. In subsequent experiments (n=3) the effect of GM-CSF (0.5 ng/mL) on the kinetics of LTB4 release after stimulation with opsonized and unopsonized III GBS was studied. The presence of GM-CSF significantly increased LTB4 release after stimulation (2.5 - 20 min) with opsonized III GBS. Peak LTB4 release occurred 15 min after stimulation (treated PMN =.973±.167 ng/mL vs. untreated PMN.208 ±.178 ng/mL; p <.005). In the absence of antibody, GM-CSF (0.5 ng/mL) had no effect on LTB4 production by N-PMN. However, at GM-CSF concentratrions of 5-10 ng/mL, LTB4 levels paralleled those released by N-PMN in the presence of GM-CSF (0.5 ng/mL) and type-specific antibody. Our data indicate that GM-CSF, at physiologically achievable concentrations, is capable of augmenting the acute inflammatory response against III GBS in the presence or absence of type-specific antibody. This is one mechanism by which GM-CSF may be useful in improving the neonatal host response to invasion by GBS.
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Valleio, J., Skeeter, C. & Edwards, M. GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR (GM-CSF) AUGMENTS LEUKOTRIENE B4 PRODUCTION BY NEONATAL NEUTROPHILS (N-PMN) STIMULATED WITH TYPE III GROUP B STREPTOCOCCUS (III GBS) ♦ 1352. Pediatr Res 41 (Suppl 4), 228 (1997). https://doi.org/10.1203/00006450-199704001-01371
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DOI: https://doi.org/10.1203/00006450-199704001-01371