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The Bacterial Peptide N-Formyl-Met-Leu-Phe Inhibits Killing of Staphylococcus epidermidis by Human Neutrophils in Fibrin Gels¹

Yongmei Li^*, John D. Loike^*, Julia A. Ember, P. Patrick Cleary, Emily Lu^*, Sadna Budhu^*, Long Cao and Samuel C. Silverstein^*

^* Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York, NY 10032; BD PharMingen, San Diego, CA 92121; Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455; and New York Blood Center, New York, NY 10021

To study human neutrophil (polymorphonuclear leukocyte (PMN)) migration and killing of bacteria in an environment similar to that found in inflamed tissues in vivo, we have used fibrin gels. Fibrin gels (1500 µm thick) containing Staphylococcus epidermidis were formed in Boyden-type chemotaxis chambers. PMN migrated <300 µm into these gels in 6 h and did not kill S. epidermidis when the gels contained heat-inactivated serum, C5-deficient serum, a streptococcal peptidase specific for a fragment of cleaved C5 (C5a), or anti-C5aR IgG. In contrast, in gels containing normal human serum, PMN migrated 1000 µm into the gels in 4 h and into the full thickness of the gels in 6 h, and killed 90% of S. epidermidis in 6 h. fMLP reduced PMN migration into fibrin gels and allowed S. epidermidis to increase by 300% in 4 h, whereas leukotriene B₄ stimulated PMN to migrate the full thickness of the gels and to kill 80% of S. epidermidis in 4 h. We conclude that both complement opsonization and C5a-stimulated chemotaxis are required for PMN bacterial killing in fibrin gels, and that fMLP inhibits PMN bactericidal activity in fibrin gels. The latter finding is surprising and suggests that in the presence of fibrin fMLP promotes bacterial virulence.

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