Mucosal IL-8 and TGF-β recruit blood monocytes: evidence for cross-talk between the lamina propria stroma and myeloid cells

Journal of Leukocyte Biology

Ronald Clements⁴  Devin Eckhoff⁴  Phillip D. Smith²  Akhil Maheshwari⁶  Lesley E. Smythies⁵  Huong L. Vu³  Lea Novak¹  L. Meg Mosteller-Barnum⁵  Marty Sellers⁵ 

[1]Pathology, and Pathology, and Pathology, and

[2]Departments of Medicine (Gastroenterology), VA Medical Center, Birmingham, Alabama Departments of Medicine (Gastroenterology), Departments of Medicine (Gastroenterology), VA Medical Center, Birmingham, Alabama VA Medical Center, Birmingham, Alabama Departments of Medicine (Gastroenterology), VA Medical Center, Birmingham, Alabama

[3]Microbiology, University of Alabama at Birmingham

[4] and Microbiology, University of Alabama at Birmingham

[5] and Microbiology, University of Alabama at Birmingham

[6] and

[7]Surgery (Gastrointestinal and Transplantation), Surgery (Gastrointestinal and Transplantation), Surgery (Gastrointestinal and Transplantation),

[8]Departments of Medicine (Gastroenterology), Departments of Medicine (Gastroenterology), Departments of Medicine (Gastroenterology),

[9]Pediatrics (Neonatology), Pediatrics (Neonatology), Pediatrics (Neonatology),

关键词: intestinal macrophage;    chemotaxis;    migration;    recruitment;    inflammation;   

DOI  :  10.1189/jlb.1005566

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

The lamina propria of the gastrointestinal mucosa contains the largest population of mononuclear phagocytes in the body, yet little is known about the cellular mechanisms that regulate mononuclear cell recruitment to noninflamed and inflamed intestinal mucosa. Here, we show that intestinal macrophages do not proliferate. We also show that a substantial proportion of intestinal macrophages express chemokine receptors for interleukin (IL)-8 and transforming growth factor-β (TGF-β), and a smaller proportion expresses receptors for N-formylmethionyl-leucyl-phenylalanine and C5a, but, surprisingly, they do not migrate to the corresponding ligands. In contrast, autologous blood monocytes, which express the same receptors, do migrate to the ligands. Blood monocytes also migrate to conditioned medium (CM) derived from lamina propria extracellular matrix, which we show contains IL-8 and TGF-β that are produced by epithelial cells and lamina propria mast cells. This migration is specific to IL-8 and TGF-β, as preincubation of the stroma-CM with antibodies to IL-8 and TGF-β significantly blocked monocyte chemotaxis to the stromal products. Together, these findings indicate that blood monocytes are the exclusive source of macrophages in the intestinal mucosa and underscore the central role of newly recruited blood monocytes in maintaining the macrophage population in noninflamed mucosa and in serving as the exclusive source of macrophages in inflamed mucosa.

【 授权许可】

Unknown