A Critical Concentration of Neutrophils is Required for Effective Bacterial Killing in Suspension

• Published in: Proceedings of the National Academy of Sciences - PNAS 2002-06, Vol.99 (12), p.8289-8294
• Main Authors: Li, Yongmei, Karlin, Arthur, Loike, John D., Silverstein, Samuel C.
• Format: Article
• Language: English
• Subjects: Bacteria; Bacterial infections; Biological Sciences; Blood; Blood Bactericidal Activity - physiology; Blood transfusion; Cells; Chemical suspensions; Colony-Forming Units Assay; Fungal infections; Fungi; Humans; In Vitro Techniques; Infections; Kinetics; Leukocytes; Mathematical constants; Medical research; Neutropenia; Neutrophils; Neutrophils - physiology; Staphylococcus epidermidis; Staphylococcus epidermidis - cytology; Staphylococcus epidermidis - growth & development; Time Factors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.122244799

We have examined the effect of neutrophil concentration on killing of a clinical isolate of Staphylococcus epidermidis. Human neutrophils at concentrations varying from 105to 107per ml were mixed in suspension with S. epidermidis at concentrations varying from 103to 108colony-forming units/ml, and the concentration of viable bacteria was assayed after various times at 37°C. The rate of bacterial killing depended on the concentration of neutrophils and not on the ratio of neutrophils to bacteria. Below a critical concentration of neutrophils, bacteria growth was greater than neutrophil killing of bacteria even when the ratio of neutrophils to bacteria was 100:1. We fitted the time course of bacterial concentration and its dependence on neutrophil concentration with an exponential function, the exponent of which is (-kp + g)t, where k is the second-order rate constant for bacterial killing, p is the neutrophil concentration, g is the first-order rate constant for bacterial growth, and t is time. We found that k ≈ 2 × 10-8ml per neutrophil per min, and g ≈ 8 × 10-3/min. Only when p is greater than g/k, which we call the critical neutrophil concentration, does the bacterial concentration fall. Under optimal assay conditions, the critical neutrophil concentration was 3-4 × 105per ml, a value very close to that (≤5 × 105per ml) known to predispose humans to bacterial and fungal infections.