“Suppressor Factor” of Neutrophils: A Short Story of a Long-Term Misconception

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I. A. Linge^1*, E. V. Kondratieva¹, T. K. Kondratieva¹, V. A. Makarov², V. I. Polshakov³, O. Yu. Savelyev³, and A. S. Apt^1*

¹Central Research Institute for Tuberculosis, 107564 Moscow, Russia; E-mail: iralinge@gmail.com, asapt@aha.ru

²Sechenov First Moscow State Medical University, Institute of Molecular Medicine, 119991 Moscow, Russia

³Lomonosov Moscow State University, Faculty of Fundamental Medicine, Center for Magnetic Tomography and Spectroscopy, 119991 Moscow, Russia

^* To whom correspondence should be addressed.

Received May 19, 2016; Revision received August 4, 2016

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A large body of evidence obtained during the last decade has demonstrated that neutrophils suppress T cell proliferation in different models of inflammation and cell interaction. The commonly used method for assessing cell proliferation and proliferation inhibition is measuring [³H]thymidine incorporation into cells. Earlier, we observed inhibition of [³H]thymidine uptake in experiments on neutrophil-mediated regulation of T cell response in tuberculosis immunity. Here, we used different types of proliferating cells to analyze the nature of the soluble “neutrophil factor” by a variety of methods (dialysis, HPLC, mass spectrometry, and NMR) and unambiguously demonstrated that neutrophils do not synthesize a specific factor inhibiting cell proliferation, but secrete high concentrations of extracellular thymidine that competitively inhibit [³H]thymidine incorporation. Although the physiological significance of thymidine secretion by neutrophils remains unknown, this phenomenon should be carefully considered when designing test systems for studying cell–cell interactions.

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KEY WORDS: neutrophils, thymidine, proliferation inhibition

DOI: 10.1134/S0006297916110067

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