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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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Antigen-induced corneal eosinophilia. Wild-type and eotaxin  mice received four subcutaneous immunizations with antigens  from the parasitic helminth O. volvulus. Animals were subsequently injected intracorneally with parasite antigen and sacrificed 1 d later. 5-μm  sections of the cornea were immunostained with rabbit sera to eosinophil  major basic protein and eosinophils in the corneal stroma were counted.  Data are shown as mean ± SEM for wild-type (n = 13) and eotaxin   (n = 14) mice with differences between groups being significant (P =  0.02).
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Figure 4: Antigen-induced corneal eosinophilia. Wild-type and eotaxin mice received four subcutaneous immunizations with antigens from the parasitic helminth O. volvulus. Animals were subsequently injected intracorneally with parasite antigen and sacrificed 1 d later. 5-μm sections of the cornea were immunostained with rabbit sera to eosinophil major basic protein and eosinophils in the corneal stroma were counted. Data are shown as mean ± SEM for wild-type (n = 13) and eotaxin (n = 14) mice with differences between groups being significant (P = 0.02).

Mentions: Eosinophils also accumulate in other tissues besides the lungs, particularly during parasitic infections. Therefore, it was of interest to determine whether a role for eotaxin could be demonstrated in other inflammatory models. Inflammation of the corneal stroma (stromal keratitis) is a serious complication of infection with the nematode parasite Onchocerca volvulus and is a major cause of blindness (River Blindness) in Africa and Latin America. After sensitization with parasite antigens in mice, intracorneal antigen challenge induces pronounced corneal inflammation associated with infiltration of the cornea by eosinophils (21). The severity of corneal pathology is correlated with the local expression of chemokines including eotaxin (12). Wild-type and eotaxin mice were immunized s.c. and then injected intracorneally with O. volvulus antigens. No difference was noted in the number of total cells in the cornea of wild-type and eotaxin mice 1 d after antigen injection (mean ± SEM/ corneal section was 870 ± 90 versus 865 ± 44, respectively; P = 0.97). In contrast, the number of eosinophils in the corneal stroma of eotaxin mice was significantly less than in wild-type mice (105 ± 21 versus 204 ± 36 eosinophils/section; P = 0.02) (Fig. 4). To determine whether this reduction persisted at later times after antigen challenge, the eosinophil recruitment 8 d after O. volvulus antigen challenge was examined. Both groups of mice now had comparable numbers of eosinophils. Eosinophils numbers were 340 ± 60 and 440 ± 55 (P = 0.26) for wild-type and eotaxin mice, respectively. These data indicate that eotaxin is important in early recruitment of eosinophils to the cornea during experimental helminth-mediated keratitis.


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)

Antigen-induced corneal eosinophilia. Wild-type and eotaxin  mice received four subcutaneous immunizations with antigens  from the parasitic helminth O. volvulus. Animals were subsequently injected intracorneally with parasite antigen and sacrificed 1 d later. 5-μm  sections of the cornea were immunostained with rabbit sera to eosinophil  major basic protein and eosinophils in the corneal stroma were counted.  Data are shown as mean ± SEM for wild-type (n = 13) and eotaxin   (n = 14) mice with differences between groups being significant (P =  0.02).
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Related In: Results  -  Collection

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Figure 4: Antigen-induced corneal eosinophilia. Wild-type and eotaxin mice received four subcutaneous immunizations with antigens from the parasitic helminth O. volvulus. Animals were subsequently injected intracorneally with parasite antigen and sacrificed 1 d later. 5-μm sections of the cornea were immunostained with rabbit sera to eosinophil major basic protein and eosinophils in the corneal stroma were counted. Data are shown as mean ± SEM for wild-type (n = 13) and eotaxin (n = 14) mice with differences between groups being significant (P = 0.02).
Mentions: Eosinophils also accumulate in other tissues besides the lungs, particularly during parasitic infections. Therefore, it was of interest to determine whether a role for eotaxin could be demonstrated in other inflammatory models. Inflammation of the corneal stroma (stromal keratitis) is a serious complication of infection with the nematode parasite Onchocerca volvulus and is a major cause of blindness (River Blindness) in Africa and Latin America. After sensitization with parasite antigens in mice, intracorneal antigen challenge induces pronounced corneal inflammation associated with infiltration of the cornea by eosinophils (21). The severity of corneal pathology is correlated with the local expression of chemokines including eotaxin (12). Wild-type and eotaxin mice were immunized s.c. and then injected intracorneally with O. volvulus antigens. No difference was noted in the number of total cells in the cornea of wild-type and eotaxin mice 1 d after antigen injection (mean ± SEM/ corneal section was 870 ± 90 versus 865 ± 44, respectively; P = 0.97). In contrast, the number of eosinophils in the corneal stroma of eotaxin mice was significantly less than in wild-type mice (105 ± 21 versus 204 ± 36 eosinophils/section; P = 0.02) (Fig. 4). To determine whether this reduction persisted at later times after antigen challenge, the eosinophil recruitment 8 d after O. volvulus antigen challenge was examined. Both groups of mice now had comparable numbers of eosinophils. Eosinophils numbers were 340 ± 60 and 440 ± 55 (P = 0.26) for wild-type and eotaxin mice, respectively. These data indicate that eotaxin is important in early recruitment of eosinophils to the cornea during experimental helminth-mediated keratitis.

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