Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor Primes Neonatal Granulocytes for Enhanced Oxidative Metabolism and Chemotaxis

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Abstract
Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) induces proliferation and differentiation of hematopoietic stem cells. Additionally, rhGM-CSF enhances the physiologic responses of adult polymorphonuclear leukocytes (PMN) especially with respect to oxidative metabolism and chemotaxis. Neonatal PMN are deficient in chemotaxis and have been demonstrated to have reduced oxidative responses in times of stress. We evaluated the priming effects of rhGMCSF (1-100 pmol/L) on cord (neonatal) superoxide production and chemotaxis. Cord and adult PMN were incubated with 100 pmol/L rhGM-CSF (Amgen, 4 × 107 U/mg) for 0-120 min and stimulated with N-formyl-1-methionyl- 1-leucyl-phenylalanine. RhGM-CSF enhanced O2− production at all time periods with maximal priming at 60 min (147.97 ± 11.14% p ≤ 0.006) with less, but significant enhancement at 120 min (116.53 ± 7.92% p ≤ 0.05). Maximal adult PMN O2− release occurred at 120 min (190.02 ± 8.71% p ≤ 0.003) and was more pronounced than cord PMN. RhGM-CSF (100 pmol/L × 30 min) incubation of cord PMN also primed for increased PMN O2− release after zymosan-activated serum stimulation (p ≤ 0.05) but not PMA (p = NS). Co-incubating cord PMNs with 100 pmol/L rhGM-CSF and a murine anti-human GM-CSF antibody (0-100 mcg/ml) resulted in 95% inhibition of the priming effect of rhGM-CSF enhancement of cord PMN (V release. RhGM-CSF, primed cord PMN for enhanced chemotaxis during early incubation (5 min) with both N-formyl-1-methionyl-l-leucyl-phenylalanine (10∼8 M) and Escherichia coli filtrate (113.54 ± 6.11% p ≤ 0.025 and 110.84 ± 4.69% p ≤ 0.001), respectively, but not at 30-min or 60-min incubation. These studies suggest that rhGM-CSF similarly primes neonatal PMN like adult PMN for enhanced in vitro PMN oxidative responses and chemotaxis.