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MIP‐1α[CCL3] acting on the CCR1 receptor mediates neutrophil migration in immune inflammation via sequential release of TNF‐α and LTB 4
Author(s) -
Ramos Cleber D. L.,
Canetti Claudio,
Souto Janeusa T.,
Silva João S.,
Hogaboam Cory M.,
Ferreira Sergio H.,
Cunha Fernando Q.
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0404237
Subject(s) - biology , inflammation , ccl3 , ccr1 , immune system , receptor , immunology , chemokine , microbiology and biotechnology , tumor necrosis factor alpha , chemokine receptor , ccl2 , biochemistry
In the present study, we investigated the involvement of macrophage‐inflammatory protein‐1α (MIP‐1α)[CC chemokine ligand 3 (CCL3)], MIP‐1β[CCL4], regulated on activation, normal T expressed and secreted (RANTES)[CCL5], and CC chemokine receptors (CCRs) on neutrophil migration in murine immune inflammation. Previously, we showed that ovalbumin (OVA)‐triggered neutrophil migration in immunized mice depends on the sequential release of tumor necrosis factor α (TNF‐α) and leukotriene B 4 (LTB 4 ). Herein, we show increased mRNA expression for MIP‐1α[CCL3], MIP‐1β[CCL4], RANTES[CCL5], and CCR1 in peritoneal cells harvested from OVA‐challenged, immunized mice, as well as MIP‐1α[CCL3] and RANTES[CCL5] but not MIP‐1β[CCL4] proteins in the peritoneal exudates. OVA‐induced neutrophil migration response was muted in immunized MIP‐1α[CCL3] −/− mice, but it was not inhibited by treatment with antibodies against RANTES[CCL5] or MIP‐1β[CCL4]. MIP‐1α[CCL3] mediated neutrophil migration in immunized mice through induction of TNF‐α and LTB 4 synthesis, as these mediators were detected in the exudates harvested from OVA‐challenged immunized wild‐type but not MIP‐1α[CCL3] −/− mice; administration of MIP‐1α[CCL3] induced a dose‐dependent neutrophil migration, which was inhibited by treatment with an anti‐TNF‐α antibody in TNF receptor 1 (p55 −/− )‐deficient mice or by MK 886 (a 5‐lipoxygenase inhibitor); and MIP‐1α[CCL3] failed to induce LTB 4 production in p55 −/− mice. MIP‐1α[CCL3] used CCR1 to promote neutrophil recruitment, as OVA or MIP‐1α[CCL3] failed to induce neutrophil migration in CCR1 −/− mice, in contrast to CCR5 −/− mice. In summary, we have demonstrated that neutrophil migration observed in this model of immune inflammation is mediated by MIP‐1α[CCL3], which via CCR1, induces the sequential release of TNF‐α and LTB 4 . Therefore, whether a similar pathway mediates neutrophil migration in human immune‐inflammatory diseases, the development of specific CCR1 antagonists might have a therapeutic potential.