Relationship between interleukin-5 and eotaxin in regulating blood and tissue eosinophilia in mice.

Abstract

The mechanism of cooperation between IL-5 and eotaxin for the selective accumulation of eosinophils at sites of allergic inflammation is unknown. In this investigation we have used IL-5 deficient mice to define the relationship between this cytokine and eotaxin in the regulation of blood eosinophilia and eosinophil homing and tissue accumulation. Both IL-5 and eotaxin could independently induce a rapid and pronounced blood eosinophilia in wild type mice when administered systemically. In contrast, only eotaxin induced a pronounced blood eosinophilia in IL-5 deficient mice. The eosinophilic response induced by intravenous eotaxin in wild type mice did not correlate with a significant reduction in the level of bone marrow eosinophils, whereas intravenous IL-5 resulted in depletion of this store. These results suggest the existence of two mechanisms by which eosinophils can be rapidly mobilized in response to intravenous eosinophil chemoattractants; first, mobilization of an IL-5 dependent bone marrow pool, and second, an eotaxin-induced sequestration of eosinophils from tissues into the blood. Subcutaneous injection of eotaxin induced a local tissue eosinophilia in wild type mice but not in IL-5 deficient mice. Furthermore, tissue eosinophilia in wild type mice, but not in IL-5 deficient mice, was enhanced by adoptive transfer of eosinophils or the administration of intravenous IL-5. However, pretreatment of IL-5 deficient mice with intraperitoneal IL-5 for 72 h restored eosinophil homing and tissue accumulation in response to subcutaneous eotaxin. We propose that eotaxin secreted from inflamed tissue may play an important role in initiating both blood and tissue eosinophilia in the early phases of allergic inflammation. Furthermore, IL-5 is not only essential for mobilizing eosinophils from the bone marrow during allergic inflammation, but also plays a critical role in regulating eosinophil homing and migration into tissues in response to eotaxin and possibly other specific chemotactic stimuli. ( J. Clin. Invest. 1997.

Resident mast cells are important for eotaxin-induced eosinophil accumulation in vivo

“…However, we have shown for the first time that the presence of a blood eosinophilia, induced by the sensitization protocol, is insufficient to support the cellular responses to eotaxin: injection of eotaxin into dorsal air-pouches of sensitized mice failed to induce an E influx but the same concentration of the chemokine was active in the peritoneal cavity, confirming our previous study [10]. It has been shown that administration of high doses of eotaxin into murine skin reduces the extent of E recruitment [12]. Therefore, in this study, lower doses of eotaxin were administered into air-pouches but again no E recruitment was elicited.…”

“…This was in contrast to the pronounced E migration observed after eotaxin injection into the peritoneal cavity of these mice [10]. Overall these studies are in agreement with reports showing that eotaxin is more effective in recruiting E s in the presence of increased numbers of circulating E s [11,12] but they also indicated that increased numbers of circulating E s per se is insufficient to obtain a cellular response to eotaxin administration.…”

“…Previous studies have established that elevated numbers of E s in the blood are essential for the effective recruitment of these cells into the tissue by eotaxin. This blood eosinophilia has been achieved with a sensitization procedure [10] or administration of IL-5 [11,12,18,19]. However, we have shown for the first time that the presence of a blood eosinophilia, induced by the sensitization protocol, is insufficient to support the cellular responses to eotaxin: injection of eotaxin into dorsal air-pouches of sensitized mice failed to induce an E influx but the same concentration of the chemokine was active in the peritoneal cavity, confirming our previous study [10].…”

“…the presence of increased levels of IL-5 [see ref . 20]), thereby rendering them more responsive to eotaxin [12]. Next, we addressed which cell type present in the mixed PCC population was playing a major role in inducing the actions of eotaxin.…”

Eotaxin Expression by Epithelial Cells and Plasma Cells in Chronic Asthma

“…Animal experimental studies lend considerable credence to the notion that eotaxin plays a pivotal role in eosinophil recruitment in allergic inflammation (Gonzalo et al, 1996(Gonzalo et al, , 1998Mould et al, 1997). These studies also provide support for the regulation of eotaxin expression by so-called Th2 cytokines, notably interleukin-13 (IL-13) (Li et al, 1999;Teran et al, 1999;Zhu et al, 1999).…”