Determination of the Critical Concentration of Neutrophils Required to Block Bacterial Growth in Tissues

We showed previously that the competition between bacterial killing by neutrophils and bacterial growth in stirred serum-containing suspensions could be modeled as the competition between a first-order reaction (bacterial growth) and a second-order reaction (bacterial killing by neutrophils). The model provided a useful parameter, the critical neutrophil concentration (CNC), below which bacterial concentration increased and above which it decreased, independent of the initial bacterial concentration. We report here that this model applies to neutrophil killing of bacteria in three-dimensional fibrin matrices and in rabbit dermis. We measured killing of 10³–10⁸ colony forming units/ml Staphylococcus epidermidis by 10⁵–10⁸ human neutrophils/ml in fibrin gels. The CNC was ∼4 × 10⁶ neutrophils/ml gel in the presence of normal serum and ∼1.6 × 10⁷ neutrophils/ml gel in the presence of C5-deficient serum. Application of our model to published data of others on killing of ∼5 × 10⁷ to 2 × 10⁸ E. coli/ml rabbit dermis yielded CNCs from ∼4 × 10⁶ to ∼8 × 10⁶ neutrophils/ml dermis. Thus, in disparate tissues and tissuelike environments, our model fits the kinetics of bacterial killing and gives similar lower limits (CNCs) to the neutrophil concentration required to control bacterial growth.