GASTROENTEROLOGY 1997;112:813 –825 Enhanced Lymphocyte Interaction in Postcapillary Venules of Peyer’s Patches During Fat Absorption in Rats YOSHIKAZU TSUZUKI,* SOICHIRO MIURA,* IWAO KUROSE,* MAKOTO SUEMATSU, ‡ HAJIME HIGUCHI,* TAKEHARU SHIGEMATSU,* HIROYUKI KIMURA,* HIROSHI SERIZAWA,* RYOTA HOKARI,* YASUTADA AKIBA,* HIDEO YAGITA, § KO OKUMURA, § PATRICK TSO, x D. NEIL GRANGER, x and HIROMASA ISHII* Departments of *Internal Medicine and ‡ Biochemistry, School of Medicine, Keio University, Tokyo, Japan; § Department of Immunology, Juntendo University, School of Medicine, Tokyo, Japan; and x Department of Physiology and Biophysics, Louisiana State University Medical Center, Shreveport, Louisiana Background & Aims: Although dietary fat is known to microscopy, we have shown that administration of olive modulate immune functions, there is a paucity of data oil significantly increases the flux of lymphocyte in intes- concerning the effects of fat absorption on migration tinal lymph. 10 Moreover, we found that absorption of of lymphocytes in intestinal lymphoid tissue. The objec- oleic acid stimulates mitogen-induced blast transforma- tive of this study was to assess the influence of fat tion of emigrated lymphocytes in intestinal lymphatics. 11 absorption on T-lymphocyte migration in Peyer’s This phenomenon appears to be related closely to the patches. Methods: T lymphocytes collected from rat formation and secretion of lipoproteins in intestinal intestinal lymph were labeled with carboxyfluorescein lymph. Although fat absorption may also affect the diacetate succinimidyl ester and injected into the jugu- movement of immune effector cells into gut-associated lar vein of recipient rats. Olive oil or octanoic acid was lymphoid tissues, little attention has been devoted to placed into the duodenum, and Peyer’s patch microcir- discerning how fat absorption might affect the kinetics culation was observed by intravital fluorescence mi- of lymphocyte migration in vivo. 12 croscopy. Results: Rolling and adherence of lympho- cytes in postcapillary venules were noted in both fasted Lymphocytes cross the endothelial lining of postcapil- and fed rats. However, lymphocyte adherence was sig- lary venules (PCVs), especially in lymph nodes and Pey- nificantly greater in olive oil–fed rats than in fasted er’s patches, where a distinct vessel morphology, termed rats. Olive oil also significantly increased the transen- high endothelial venules (HEVs), characterizes the sites dothelial migration of T lymphocytes. Octanoic acid of intense lymphocyte traffic. 13–15 The interaction of ad- stimulated lymphocyte rolling but did not affect lympho- hesion molecules on the surface of lymphocytes with cyte adherence. Olive oil enhanced the expression of counter-receptors on endothelial cells allows for the mi- both a 4 -integrin and L-selectin on lymphocytes, gration of lymphocytes in a tissue-specific manner. 16,17 whereas octanoic acid only increased the expression In several species, it has been shown that molecules be- of L-selectin. Conclusions: Lymphocyte rolling and ad- longing to the immunoglobulin (Ig) superfamily, the herence are enhanced by olive oil feeding, possibly integrin family, and the selectin family mediate the inter- through an interaction between activated adhesion molecules on lymphocytes and counter-receptors on actions between lymphocytes and endothelial cells. L- endothelial cells. Selectin, 18 CD44, 19 and a 4 /b 7 or b 1 -integrins 20,21 are be- lieved to function as organ-specific homing receptors for lymphocytes. C Novo et al. 12 showed that in vitro – induced alterations onsiderable effort has been directed at defining the influence of nutrition on the immune system. 1–3 For in the fatty acid composition of lymphocyte membranes, example, there is considerable evidence that implicates dietary fat as a modulator of different immune func- Abbreviations used in this paper: CFDASE, carboxyfluorescein diac- tions. 4–6 This contention is supported by several reports etate succinimidyl ester; CSFE, carboxyfluorescein succinimidyl es- showing in vitro and in vivo actions of saturated and ter; FACS, fluorescein-activated cell sorter; FITC, fluorescein isothio- unsaturated fatty acids on lymphocyte function, although cyanate; HEV, high endothelial venule; ICAM, intercellular adhesion molecule; LEC, lymphocyte-endothelial cell; LFA, lymphocyte func- the effects of specific forms of dietary fat on the immune tion–activated antigen; MAb, monoclonal antibody; PCV, postcapil- system remain controversial. 6–9 A dependence of lym- lary venule. phocyte function in intestinal lymphatics on lipid ab- q 1997 by the American Gastroenterological Association 0016-5085/97/$3.00 sorption has been proposed. 10,11 Using intravital video- / 5e19$$0011 02-17-97 21:58:25 gasa WBS-Gastro