Abstract
Whether or not IL-8 attracts T lymphocytes and activates neutrophils in vivo remains unclear. Most studies on function of IL-8 in vivo have been done on human IL-8 in heterologous animals. To elucidate the role of IL-8 in vivo, we injected homologous IL-8 into rabbit knee joints and investigated the inflammatory response. Injection of 10°μg of rabbit IL-8 induced a massive accumulation of neutrophils. IL-8 attracts T lymphocytes in vitro; however, rabbit IL-8 induced no appreciable lymphocyte accumulation in rabbits. Although human IL-8 was reported not to induce cartilage destruction when injected into heterologous animals, we observed that rabbit IL-8 did provoke a release of neutrophil elastase, leading to cartilage destruction, when injected into rabbits. An inhibitor against neutrophil elastase (ONO-5046) prevented destruction of the cartilage. Injection of rabbit IL-8 induced bioactive and immunoreactive IL-1β and IL-1 receptor antagonist (IL-1Ra) in the joint cavity. Immunohistochemistry showed that IL-1β and IL-IRa positive cells were infiltrating leukocytes. In neutrophil-depleted rabbits, rabbit IL-8 induced far lesser concentrations of IL-1β and IL-1Ra and no cartilage destruction compared with findings in normal rabbits. Thus, the infiltrating neutrophils are the main producers of these cytokines and are responsible for the cartilage destruction. In addition to neutrophil chemotactic activity, IL-8 proved to have a neutrophil-activating capability in vivo, with respect to release of neutrophil elastase and induction of IL-1β and IL-1Ra.
| Original language | English |
|---|---|
| Pages (from-to) | 5418-5425 |
| Number of pages | 8 |
| Journal | Journal of Immunology |
| Volume | 154 |
| Issue number | 10 |
| Publication status | Published - 1995 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
Cite this
Neutrophil accumulation and activation by homologous IL-8 in rabbits : IL-8 Induces destruction of cartilage and production of IL-1 and IL-1 receptor antagonist in vivo. / Matsukawa, Akihiro; Yoshimura, Teizo; Maeda, Takako; Ohkawara, Susumu; Takagi, Katsumasa; Yoshinaga, Masaru.
In: Journal of Immunology, Vol. 154, No. 10, 1995, p. 5418-5425.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Neutrophil accumulation and activation by homologous IL-8 in rabbits
T2 - IL-8 Induces destruction of cartilage and production of IL-1 and IL-1 receptor antagonist in vivo
AU - Matsukawa, Akihiro
AU - Yoshimura, Teizo
AU - Maeda, Takako
AU - Ohkawara, Susumu
AU - Takagi, Katsumasa
AU - Yoshinaga, Masaru
PY - 1995
Y1 - 1995
N2 - Whether or not IL-8 attracts T lymphocytes and activates neutrophils in vivo remains unclear. Most studies on function of IL-8 in vivo have been done on human IL-8 in heterologous animals. To elucidate the role of IL-8 in vivo, we injected homologous IL-8 into rabbit knee joints and investigated the inflammatory response. Injection of 10°μg of rabbit IL-8 induced a massive accumulation of neutrophils. IL-8 attracts T lymphocytes in vitro; however, rabbit IL-8 induced no appreciable lymphocyte accumulation in rabbits. Although human IL-8 was reported not to induce cartilage destruction when injected into heterologous animals, we observed that rabbit IL-8 did provoke a release of neutrophil elastase, leading to cartilage destruction, when injected into rabbits. An inhibitor against neutrophil elastase (ONO-5046) prevented destruction of the cartilage. Injection of rabbit IL-8 induced bioactive and immunoreactive IL-1β and IL-1 receptor antagonist (IL-1Ra) in the joint cavity. Immunohistochemistry showed that IL-1β and IL-IRa positive cells were infiltrating leukocytes. In neutrophil-depleted rabbits, rabbit IL-8 induced far lesser concentrations of IL-1β and IL-1Ra and no cartilage destruction compared with findings in normal rabbits. Thus, the infiltrating neutrophils are the main producers of these cytokines and are responsible for the cartilage destruction. In addition to neutrophil chemotactic activity, IL-8 proved to have a neutrophil-activating capability in vivo, with respect to release of neutrophil elastase and induction of IL-1β and IL-1Ra.
AB - Whether or not IL-8 attracts T lymphocytes and activates neutrophils in vivo remains unclear. Most studies on function of IL-8 in vivo have been done on human IL-8 in heterologous animals. To elucidate the role of IL-8 in vivo, we injected homologous IL-8 into rabbit knee joints and investigated the inflammatory response. Injection of 10°μg of rabbit IL-8 induced a massive accumulation of neutrophils. IL-8 attracts T lymphocytes in vitro; however, rabbit IL-8 induced no appreciable lymphocyte accumulation in rabbits. Although human IL-8 was reported not to induce cartilage destruction when injected into heterologous animals, we observed that rabbit IL-8 did provoke a release of neutrophil elastase, leading to cartilage destruction, when injected into rabbits. An inhibitor against neutrophil elastase (ONO-5046) prevented destruction of the cartilage. Injection of rabbit IL-8 induced bioactive and immunoreactive IL-1β and IL-1 receptor antagonist (IL-1Ra) in the joint cavity. Immunohistochemistry showed that IL-1β and IL-IRa positive cells were infiltrating leukocytes. In neutrophil-depleted rabbits, rabbit IL-8 induced far lesser concentrations of IL-1β and IL-1Ra and no cartilage destruction compared with findings in normal rabbits. Thus, the infiltrating neutrophils are the main producers of these cytokines and are responsible for the cartilage destruction. In addition to neutrophil chemotactic activity, IL-8 proved to have a neutrophil-activating capability in vivo, with respect to release of neutrophil elastase and induction of IL-1β and IL-1Ra.
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UR - http://www.scopus.com/inward/citedby.url?scp=0029020005&partnerID=8YFLogxK
M3 - Article
C2 - 7730643
AN - SCOPUS:0029020005
VL - 154
SP - 5418
EP - 5425
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 10
ER -