How many neutrophils are enough (redux, redux)?
Samuel C. Silverstein, Raul Rabadan
Samuel C. Silverstein, Raul Rabadan
Published August 1, 2012; First published July 23, 2012
Citation Information: J Clin Invest. 2012;122(8):2776-2779. https://doi.org/10.1172/JCI63939.
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Category: Commentary

How many neutrophils are enough (redux, redux)?

Abstract

Many chemotherapeutic regimens produce neutropenia, which predisposes to microbial infection. However, not all neutropenic individuals develop infections, so the ability to predict this outcome would be a powerful clinical tool. In this issue of the JCI, Malka et al. describe a dynamic system model of neutrophil bactericidal activity that confirms and extends the concept of critical neutrophil concentration. The authors demonstrate that when the neutrophil concentration approaches the critical concentration, bacterial populations in contact with them exhibit bistability. Their experimental findings raise the intriguing possibility of greater variability in bactericidal activity of neutrophils from healthy adults than heretofore recognized; their model predicts that this could have life-and-death consequences.

Authors

Samuel C. Silverstein, Raul Rabadan

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Figure 1

Comparative behaviors of bacterial populations at or near the CNC, as predicted by the equations of Li et al.

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Comparative behaviors of bacterial populations at or near the CNC, as pr...
(20, 21) and Malka et al. (25). (A) Li et al. derived an equation that includes an experimentally determined bacterial killing constant and the bacterial growth rate (20, 21). It predicts the CNC is constant at all B values. Their experiments show, however, that the bacterial growth rate and killing constant decrease, and the CNC increases (curved dashed line), at B values greater than 107 CFU/ml in stirred suspension and greater than 106 CFU/ml in fibrin gel (not shown). Most importantly, this equation predicts B will decrease or increase at all N values below or above the CNC, respectively, and remain constant at the CNC. (B) In contrast, as reported here by Malka et al., the bacterial population is bistable at N at or very near the CNC, creating favorable conditions for uncontrolled bacterial growth (25). N1 and N2 and the dashed line indicate the N and B values that define the zone of bistability in the bacterial population. For N below the CNC (solid yellow line), the bacterial population grows exponentially. Note also that in fibrin gels and rabbit dermis, the CNC at all N values is at least 2-fold larger than in stirred suspensions, a reflection of the effect of the former environment on the bacterial killing constant.