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This Article Full Text Full Text (PDF) Extended Methods All Versions of this Article: jimmunol.0900409v1 183/2/1155    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Carlow, D. A. Articles by Ziltener, H. J. PubMed PubMed Citation Articles by Carlow, D. A. Articles by Ziltener, H. J. Pubmed/NCBI databases Substance via MeSH

Lymphocytes in the Peritoneum Home to the Omentum and Are Activated by Resident Dendritic Cells¹

Douglas A. Carlow^2,*, Michael R. Gold and Hermann J. Ziltener^*

^* The Biomedical Research Centre and the Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada; and The Department of Microbiology and Immunology and the Infection, Inflammation, and Immunity (I3) Research Group, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada

The omentum is of interest in the context of obesity-related metabolic disease where adipose tissue exhibits inflammatory changes; however, the immunology of the omentum is underexplored. The greater omentum is draped from the stomach and consists predominantly of adipose tissue studded with lymphoreticular aggregations (milky spots) that distinguish it from other visceral adipose tissues. Milky spots are thought to contain and conduct leukocytes in transit from the blood to the peritoneal cavity, particularly during peritonitis. We show here that both B and T lymphocytes counterflow from the peritoneal cavity to the omentum in mice. Residence in the omentum was brief with a t_1/2 residence time of 6 h. Omentum access was pertussis toxin-sensitive, dependent on activation of the Rap1 GTPase, and on the integrin LFA-1. B cells and CD44^high T cells accessed the omentum most efficiently, but homing of resting CD44^low T cells was also observed. Omental tissue from normal healthy mice was found to contain CD8^–CD11b^highMHC class II^highCD11c^high dendritic cells that promoted the rapid activation of T cells entering the omentum and cross-presented soluble OVA or OVA acquired from either OVA-expressing Escherichia coli or OVA-pulsed spleen cells. We conclude that the omentum incorporates two key features of immunological sentinel function, actively supported lymphocyte traffic and dendritic cells, that reinforce a conceptual framework for function in stimulating adaptive immunity. These results extend basic understanding of omental and peritoneal cavity immunology and of how proinflammatory events occurring within the peritoneal cavity might affect adipocyte and hepatocyte metabolism.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Funding for this work was provided through research grant MOP-77552 to H.J.Z. from the Canadian Institutes for Health Research (CIHR).

² Address correspondence and reprint requests to Dr. Douglas A. Carlow, The Biomedical Research Centre, 2222 Health Sciences Mall, University of British Columbia, Vancouver, B.C. V6T 1Z3, Canada. E-mail address: doug{at}brc.ubc.ca

³ Abbreviations used in this paper: PC, peritoneal cavity; CTO, CellTracker Orange; DC, dendritic cell; MHC-II, MHC class II; OFB, omental fat band; Rap-GAPII, Rap-specific GTPase-activating protein II.

⁴ The online version of the article contains Extended Methods.