Published online before print July 20, 2006

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1005566

Received for publication October 4, 2005.
Revised March 7, 2006.
Accepted for publication April 6, 2006.

Article

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

Lesley E. Smythies ^*@, Akhil Maheshwari , Ronald Clements , Devin Eckhoff , Lea Novak , Huong L. Vu ^¶, L. Meg Mosteller-Barnum ^*, Marty Sellers ^*, and Phillip D. Smith ^*||

Departments of *Medicine (Gastroenterology), Pediatrics (Neonatology), Surgery (Gastrointestinal and Transplantation), Pathology, and ^¶Microbiology, University of Alabama at Birmingham; and ^||VA Medical Center, Birmingham, Alabama

^@ To whom correspondence should be addressed. E-mail: lesmy{at}uab.edu.

Abstract

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- (TGF-), and a smaller proportion expresses receptors for N-formylmethionyl-leucyl-phenylalanine and C5a, but it is surprising that 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-, which are produced by epithelial cells and lamina propria mast cells. This migration is specific to IL-8 and TGF-, as preincubation of the stroma-CM with antibodies to IL-8 and TGF- 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.

Key Words: intestinal macrophage • chemotaxis • migration • recruitment • inflammation

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