Neutrophil recruitment in immunized mice depends on MIP‐2 inducing the sequential release of MIP‐1α, TNF‐α and LTB4

• Published in: European journal of immunology Vol. 36; no. 8; pp. 2025 - 2034
• Main Authors: Ramos, Cleber D. L., Fernandes, Karla S. S., Canetti, Claudio, Teixeira, Mauro M., Silva, João S., Cunha, Fernando Q.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01-08-2006
• Subjects: Autoimmunity; Chemokines; Neutrophils
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200636057

Neutrophils are thought to play an important role in the tissue damage observed in various autoimmune diseases. Chemokines, cytokines and leukotrienes have recognized roles in the orchestration of neutrophil migration. We have recently shown that antigen‐induced neutrophil migration into the peritoneum of immunized mice is mediated by macrophage‐inflammatory protein (MIP)‐1α which interacts with CCR1 and induces the sequential release of TNF‐α and leukotriene B4 (LTB4). The present study investigates the role of MIP‐2 and CXCR2 in the cascade of events leading to mediator generation and neutrophil influx. Antigen challenge of immunized mice induced the expression of CXCR2 and the production of KC and MIP‐2 proteins. Antigen‐induced neutrophil migration was inhibited by a CXCR2 receptor antagonist (repertaxin) or an anti‐MIP‐2 antibody, but not by an anti‐KC antibody. Administration of MIP‐2 promoted a dose‐dependent neutrophil migration in naive mice which was inhibited by repertaxin, anti‐TNF‐α, anti‐MIP‐1α antibodies or by MK886 (leukotriene synthesis inhibitor). MIP‐2 administration induced the release of MIP‐1α, TNF‐α and LTB4, and the release of the latter two was inhibited by anti‐MIP‐1α antibody treatment. Our studies highlight the intricate balance between mediator production and action during an immune‐mediated inflammatory response and suggest a mediator cascade leading to neutrophil influx following antigen challenge of immunized mice: MIP‐2 → MIP‐1α → TNF‐α → LTB4.