Quantitative comparison of C-X-C chemokines produced by endotoxin-stimulated human alveolar macrophages

被引:45
作者
Goodman, RB
Strieter, RM
Frevert, CW
Cummings, CJ
Tekamp-Olson, P
Kunkel, SL
Walz, A
Martin, TR
机构
[1] Vet Affairs Med Ctr, Pulm & Crit Care Med Sect, Med Res Serv, Seattle, WA 98108 USA
[2] Univ Washington, Sch Med, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98108 USA
[3] Univ Michigan, Sch Med, Dept Med, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA
[4] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA
[5] Univ Bern, Theodor Kocher Inst, CH-3000 Bern 9, Switzerland
[6] Chiron Corp, Emeryville, CA 94608 USA
关键词
chemotaxis; monocytes; neutrophils; lung;
D O I
10.1152/ajplung.1998.275.1.L87
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The C-X-C chemokines are a structurally related and functionally redundant family of proteins with neutrophil chemotactic activity. Many of the C-X-C chemokines are produced by endotoxin-stimulated alveolar macrophages (AMs), but knowledge of their relative quantities and their relative contributions to the total chemotactic activity released from these cells is incomplete. Human AMs were stimulated with or without Escherichia coli endotoxin for 2, 4, 8, and 24 h. The mRNA sequences of interleukin (IL)-8, the 78-amino acid epithelial cell-derived neutrophil activator (ENA-78), growth-related protein (GRO) alpha, GRO beta, and GRO gamma were cloned by PCR and identified by sequence analysis. The relative mRNA quantities were compared by Northern analysis, and IL-8 was found to predominate. Similarly, IL-8 protein concentrations in the cell supernatants were consistently higher than either the ENA-78 or GRO concentration, and by 24 h, IL-8 concentrations were 10-fold higher than those of the other C-X-C chemokines. Blocking polyclonal antibodies to IL-8 substantially reduced the chemotactic activity in the AM supernatants, whereas antibodies to ENA-78 and GRO had little or no effect. We conclude that IL-8 is the predominant C-X-C chemokine and the dominant neutrophil chemoattractant accumulating in 24-h supernatants of lipopolysaccharide-stimulated human AMs. These studies provide insight into potentially effective strategies of interrupting AM-derived inflammatory signals in the lungs.
引用
收藏
页码:L87 / L95
页数:9
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