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Transient Neutropenia: Neutrophil Distribution and Replacement

Departments of Radiology, Pathology and Cell Biology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania

Correspondence: For correspondence or reprints contact: Mathew L. Thakur, PhD, Department of Radiology, Thomas Jefferson University Hospital, 1020 Locust St., Rm. 359, Philadelphia, PA 19107.

ABSTRACT

Radiolabeled polymorphonuclear (PMN) receptor-specific proteins or peptides lead the list of agents being evaluated for imaging inflammatory foci. Some of these agents induce transient neutropenia. This study was designed to quantify the degree of dose dependency of neutropenia, determine the duration of neutropenia, identify the organs in which these PMNs sequester and ascertain if these PMNs return to the circulation. Methods: Rodent anti-PMN (Gr-1) MAb RB6-8C5 (IgG-2a) and Balb/c mice served as the model, and PMN nonspecific ME 31.3 (IgG-2a) as a control. Circulating PMN number was determined several times, 30 min prior to and between 1 min and 120 hr after MAb administration. Iodine-125-MAbs provided quantification of circulating activity and tissue distribution as a function of time. Results: Data showed the severity of neutropenia increased with the amount of MAb administered (>95% PMNs lost after 150 µg versus <85% after 10 µg). Moreover, the recovery time for PMN counts to reach the pretreatment level also increased in a dose-dependent manner (96 hr at 150 µg versus 4 hr at 10 µg and 2 hr at 2 µg). The blood activity, however, which declined quickly with the neutropenia, never rose again with PMN recovery. As a function of time, radioactivity in the study group decreased from all organs except from the liver and spleen, whereas in the control group, it decreased from all organs, including the liver and spleen (e.g., 4 hr liver, 29.4% decrease versus 91.2% decrease in the control group; and spleen, 15.5% decrease versus 63.6% decrease in control group). Conclusion: The degree and duration of neutropenia is dose-dependent. PMNs, lost from the circulation, sequester in the reticuloendothelial system, and do not return to circulation. Therefore, they are not available to image inflammatory foci. The PMN concentration is restored to a pretreatment level in a dose-dependent fashion, presumably by freshly released PMNs from bone marrow.

Key Words: polymorphonuclear receptor-specific proteins • neutropenia • dose-dependency

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