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Ccl2 and Ccl3 mediate neutrophil recruitment through induction of protein synthesis and secondary generation of lipid mediators
Author(s) -
Reichel Christoph Andreas,
Rehberg Markus,
Lerchenberger Max,
Berberich Nina,
Bihari Peter,
Zahler Stefan,
Krombach Fritz
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.762.11
Subject(s) - ccl3 , chemokine , ccl2 , intravital microscopy , chemotaxis , integrin alpha m , chemistry , inflammation , microbiology and biotechnology , in vivo , immunology , flow cytometry , biology , biochemistry , receptor
CC chemokines Ccl2 and Ccl3 have recently been implicated in neutrophil migration. Here, we analyzed the role of endogenously generated lipid mediators for neutrophil recruitment in Ccl2‐ and Ccl3‐elicited inflammation in the mouse cremaster muscle using in vivo microscopy. Stimulation with Ccl2 and Ccl3 induced a significant increase in numbers of firmly adherent and transmigrated leukocytes (> 80% Gr‐1 + neutrophils) as compared to controls, respectively. This increase was significantly attenuated in mice receiving inhibitors of RNA synthesis (actinomycin D) as well as antagonists of PAF (BN52021) and LTB 4 (MK‐886). In contrast, leukocyte responses elicited by PAF and LTB 4 themselves were not affected by actinomycin D, BN52021, or MK‐886. Conversely, PAF and LTB 4 , but not Ccl2 and Ccl3, induced shedding of CD62L and increased expression of CD11b on neutrophils as assessed by flow cytometry. Moreover, Ccl2‐ and Ccl3‐elicited leakage of FITC dextran as well as collagen IV remodeling within the venular basement membrane (BM) were completely absent in neutropenic mice. These data demonstrate that Ccl2‐ and Ccl3‐elicited firm adherence and (subsequent) transmigration of neutrophils require protein synthesis and secondary generation of lipid mediators such as PAF and LTB 4 which in turn directly activate neutrophils. Thereby, neutrophils facilitate BM remodeling and promote the microvascular leakage.