Human Skin Mast Cells Express Complement Factors C3 and C5

被引:28
|
作者
Fukuoka, Yoshihiro [1 ]
Hite, Michelle R. [1 ]
Dellinger, Anthony L. [1 ]
Schwartz, Lawrence B. [1 ]
机构
[1] Virginia Commonwealth Univ, Dept Internal Med, Div Rheumatol Allergy & Immunol, Richmond, VA 23298 USA
来源
JOURNAL OF IMMUNOLOGY | 2013年 / 191卷 / 04期
基金
美国国家卫生研究院;
关键词
TUMOR-NECROSIS-FACTOR; FC-EPSILON-RI; FACTOR-B; RECOMBINANT HUMAN; AIRWAY HYPERRESPONSIVENESS; ULTRASTRUCTURAL ANALYSIS; PROTEIN-BIOSYNTHESIS; CYTOKINE REGULATION; SIGNALING PATHWAYS; ASTHMATIC RESPONSE;
D O I
10.4049/jimmunol.1202889
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We examine whether complement factor C3 or C5 is synthesized by human skin-derived mast cells and whether their synthesis is regulated by cytokines. C3 and C5 mRNAs were assessed by RT-PCR, and proteins by flow cytometry, confocal microscopy, Western blotting, and ELISA. C3 and C5 mRNAs were each expressed, and baseline protein levels/10(6) cultured mast cells were 0.9 and 0.8 ng, respectively, and located in the cytoplasm outside of secretory granules. C3 accumulated in mast cell culture medium over time and by 3 d reached a concentration of 9.4 +/- 8.0 ng/ml, whereas C5 levels were not detectable (<0.15 ng/ml). Three-day incubations of mast cells with IL-1 alpha, IL-1 beta, IL-17, IFN-gamma, IL-6, or anti-Fc epsilon RI did not affect C3 protein levels in culture medium, whereas incubations with PMA, TNF-alpha, IL-13, or IL-4 enhanced levels of C3 1.7- to 3.3-fold. In contrast with C3, levels of C5 remained undetectable. Importantly, treatment with TNF-alpha together with either IL-4 or IL-13 synergistically enhanced C3 (but not C5) production in culture medium by 9.8- or 7.1-fold, respectively. This synergy was blocked by attenuating the TNF-alpha pathway with neutralizing anti-TNF-alpha Ab, soluble TNFR, or an inhibitor of NF-kappa B, or by attenuating the IL-4/13 pathway with Jak family or Erk antagonists. Inhibitors of PI3K, Jnk, and p38 MAPK did not affect this synergy. Thus, human mast cells can produce and secrete C3, whereas beta-tryptase can act on C3 to generate C3a and C3b, raising the likelihood that mast cells engage complement to modulate immunity and inflammation in vivo.
引用
收藏
页码:1827 / 1834
页数:8
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