Peripheral blood eosinophilia in owl monkeys is associated with increased eosinophilopoiesis yet depressed recruitment kinetics to the Chemokine RANTES

Abstract

New world nonhuman primates of the genus Aotus (owl monkeys) can be categorized by 11 distinct karyotypes (K). It has been demonstrated that monkeys of K-VI persistently have one order of magnitude more eosinophils (EOS) in the peripheral blood than K-I monkeys. The purpose of this study was to investigate the basis for this difference and examine EOS recruitment using two cutaneous models of inflammation. Peripheral blood EOS were isolated on metrizamide gradients to > or = 95% purity and then used for phenotypic studies. There were no significant differences when comparing karyotypes in the ratio of normodense (K-I, 6.4% +/- 3.8%; K-VI, 21.1% +/- 8.8%) EOS or their survival in culture (K-I, 5.3% +/- 2.9% at 72 hours; K-VI, 2.8% +/- 0.7% at 72 hours) (P > .05). Examination of bone marrow revealed that K-VI monkeys had greater than fivefold more EOS and EOS precursors than K-I animals. To examine EOS function in recruitment, monkeys of each karyotype were given a single intradermal injection of Escherichia coli lipopolysaccharide (LPS) or human recombinant (PMN) and mononuclear cells occurred in response to LPS as early as 4 hours after injection; the severity of infiltration was similar in both karyotypes and at all time points up to 24 hours. In contrast, by 8 hours after intradermal injection of RANTES, leukocyte infiltration in K-I monkeys consisted mostly of PMN (94.8% +/- 0.7%) that were predominantly EOS. In comparison, there was essentially no infiltrate in K-VI animals at all time points. There was no difference in VCAM-1 expression in response to intradermal LPS or RANTES between the two karyotypes. These results suggest that the genetic basis of peripheralblood eosinophilia in K-VI owl monkeys is likely a function of heightened eosinophilopoiesis and depressed recruitment kinetics from the peripheral circulatory pool in response to RANTES.