TRANSIENT NEUTROPENIA - NEUTROPHIL DISTRIBUTION AND REPLACEMENT

Radiolabeled polymorphonuclear (PMN) receptor-specific proteins or pep tides lead the list of agents being evaluated for imaging inflammatory foci, Some of these agents induce transient neutropenia, This study w as designed to quantify the degree of dose dependency of neutropenia, determine the duration of neutropenia, identify the organs in which th ese PMNs sequester and ascertain if these PMNs return to the circulati on, Methods: Rodent anti-PMN (Gr-1) MAb RB6-8C5 (IgG-2a) and Balb/c mi ce sewed as the model, and PMN nonspecific ME 31.3 (IgG-2a) as a contr ol. Circulating PMN number was determined several times, 30 min prior to and between 1 min and 120 hr after MAb administration. Iodine-125-M Abs provided quantification of circulating activity and tissue distrib ution as a function of time. Results: Data showed the severity of neut ropenia increased with the amount of MAb administered (>95% PMNs lost after 150 mu g versus <85% after 10 mu g). Moreover, the recovery time for PMN counts to reach the pretreatment level also increased in a do se-dependent manner (96 hr at 150 mu g versus 4 hr at 10 mu g and 2 hr at 2 mu g). 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 excep t from the liver and spleen, whereas in the control group, it decrease d from all organs, including the liver and spleen (e.g., 4 hr liver, 2 9.4% decrease versus 91.2% decrease in the control group; and spleen, 15.5% decrease versus 63.6% decrease in control group). Conclusion: Th e degree and duration of neutropenia is dose-dependent, PMNs, lost fro m 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 pretreatmen t level in a dose-dependent fashion, presumably by freshly released PM Ns from bone marrow.