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Targeted disruption of the chemokine eotaxin partially reduces antigen-induced tissue eosinophilia.

Rothenberg ME, MacLean JA, Pearlman E, Luster AD, Leder P - J. Exp. Med. (1997)

Bottom Line: Furthermore, it remains unclear why there is constitutive expression of eotaxin in healthy states in the absence of eosinophilic inflammation.To begin to determine the significance of eotaxin at baseline and during eosinophil-mediated disease processes, we have used targeted gene disruption to generate mice that are deficient in eotaxin.These results indicate a contributory role for eotaxin in the generation of peripheral blood and antigen-induced tissue eosinophilia.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.

ABSTRACT
The chemokines are a large group of chemotactic cytokines that regulate leukocyte trafficking and have recently been shown to inhibit human immunodeficiency virus entry into cells. Eotaxin is a C-C chemokine implicated in the recruitment of eosinophils in a variety of inflammatory disorders and, unlike all other eosinophil chemoattractants, is eosinophil specific. However, given the large number of chemoattractants that have activities on eosinophils, it is unclear whether eotaxin has an important role in vivo. Furthermore, it remains unclear why there is constitutive expression of eotaxin in healthy states in the absence of eosinophilic inflammation. To begin to determine the significance of eotaxin at baseline and during eosinophil-mediated disease processes, we have used targeted gene disruption to generate mice that are deficient in eotaxin. Such mice demonstrate that eotaxin enhances the magnitude of the early (but not late) eosinophil recruitment after antigen challenge in models of asthma and stromal keratitis. Surprisingly, a role for eotaxin in regulating the constitutive number of eosinophils in the peripheral circulation is also demonstrated. These results indicate a contributory role for eotaxin in the generation of peripheral blood and antigen-induced tissue eosinophilia.

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Eosinophil count in the peripheral blood of naive mice. The  absolute eosinophil count in the peripheral blood is shown for wild-type  (+/+) and eotaxin  (−/−) mice. The results are expressed as mean ±  SEM for +/+ (n = 12) and −/− (n = 14); P = 0.007.
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Figure 2: Eosinophil count in the peripheral blood of naive mice. The absolute eosinophil count in the peripheral blood is shown for wild-type (+/+) and eotaxin (−/−) mice. The results are expressed as mean ± SEM for +/+ (n = 12) and −/− (n = 14); P = 0.007.

Mentions: One of the characteristic features of eotaxin that remains puzzling is its widespread (although not ubiquitous) constitutive expression in various tissues, especially lymphoid tissue (thymus and lymph node). It has been postulated that constitutive eotaxin might affect eosinophil and/or lymphocyte homing into these tissues (6). Therefore it was of interest to examine various organs and their resident leukocyte populations. Peripheral blood analysis revealed no abnormalities in the total leukocyte, red blood cell, and platelet counts, or white blood cell differential in eotaxin mice compared with wild type mice (data not shown). In contrast, the total eosinophil count was significantly reduced (P = 0.007) in the knockout mice compared with wild-type mice (Fig. 2). Wildtype mice and mice had 243 ± 43 (mean ± SEM, n = 12) and 69 ± 22 (n = 13) eosinophils/mm3 of blood, respectively. Analysis of bone marrow cells revealed no differences in the eosinophil lineage (data not shown). This indicated that eotaxin was unlikely to be stimulating eosinophil hematopoiesis as might have been expected based on the ability of other chemokines (e.g., MIP-1α, IL-8) to regulate hematopoiesis (22).


Targeted disruption of the chemokine eotaxin partially reduces antigen-induced tissue eosinophilia.

Rothenberg ME, MacLean JA, Pearlman E, Luster AD, Leder P - J. Exp. Med. (1997)

Eosinophil count in the peripheral blood of naive mice. The  absolute eosinophil count in the peripheral blood is shown for wild-type  (+/+) and eotaxin  (−/−) mice. The results are expressed as mean ±  SEM for +/+ (n = 12) and −/− (n = 14); P = 0.007.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196140&req=5

Figure 2: Eosinophil count in the peripheral blood of naive mice. The absolute eosinophil count in the peripheral blood is shown for wild-type (+/+) and eotaxin (−/−) mice. The results are expressed as mean ± SEM for +/+ (n = 12) and −/− (n = 14); P = 0.007.
Mentions: One of the characteristic features of eotaxin that remains puzzling is its widespread (although not ubiquitous) constitutive expression in various tissues, especially lymphoid tissue (thymus and lymph node). It has been postulated that constitutive eotaxin might affect eosinophil and/or lymphocyte homing into these tissues (6). Therefore it was of interest to examine various organs and their resident leukocyte populations. Peripheral blood analysis revealed no abnormalities in the total leukocyte, red blood cell, and platelet counts, or white blood cell differential in eotaxin mice compared with wild type mice (data not shown). In contrast, the total eosinophil count was significantly reduced (P = 0.007) in the knockout mice compared with wild-type mice (Fig. 2). Wildtype mice and mice had 243 ± 43 (mean ± SEM, n = 12) and 69 ± 22 (n = 13) eosinophils/mm3 of blood, respectively. Analysis of bone marrow cells revealed no differences in the eosinophil lineage (data not shown). This indicated that eotaxin was unlikely to be stimulating eosinophil hematopoiesis as might have been expected based on the ability of other chemokines (e.g., MIP-1α, IL-8) to regulate hematopoiesis (22).

Bottom Line: Furthermore, it remains unclear why there is constitutive expression of eotaxin in healthy states in the absence of eosinophilic inflammation.To begin to determine the significance of eotaxin at baseline and during eosinophil-mediated disease processes, we have used targeted gene disruption to generate mice that are deficient in eotaxin.These results indicate a contributory role for eotaxin in the generation of peripheral blood and antigen-induced tissue eosinophilia.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.

ABSTRACT
The chemokines are a large group of chemotactic cytokines that regulate leukocyte trafficking and have recently been shown to inhibit human immunodeficiency virus entry into cells. Eotaxin is a C-C chemokine implicated in the recruitment of eosinophils in a variety of inflammatory disorders and, unlike all other eosinophil chemoattractants, is eosinophil specific. However, given the large number of chemoattractants that have activities on eosinophils, it is unclear whether eotaxin has an important role in vivo. Furthermore, it remains unclear why there is constitutive expression of eotaxin in healthy states in the absence of eosinophilic inflammation. To begin to determine the significance of eotaxin at baseline and during eosinophil-mediated disease processes, we have used targeted gene disruption to generate mice that are deficient in eotaxin. Such mice demonstrate that eotaxin enhances the magnitude of the early (but not late) eosinophil recruitment after antigen challenge in models of asthma and stromal keratitis. Surprisingly, a role for eotaxin in regulating the constitutive number of eosinophils in the peripheral circulation is also demonstrated. These results indicate a contributory role for eotaxin in the generation of peripheral blood and antigen-induced tissue eosinophilia.

Show MeSH
Related in: MedlinePlus