Enteral feeding preserves mucosal immunity despite in vivo MAdCAM-1 blockade of lymphocyte homing.
OBJECTIVE
To determine the influence of route of nutrition on gut mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) expression and the effect of MAdCAM-1 blockade on gut-associated lymphoid tissue (GALT) lymphocyte populations and established respiratory antibacterial immunity.


BACKGROUND
Lymphocytes, sensitized to antigens in Peyer's patches, migrate via mesenteric lymph nodes and home to intestinal lamina propria. MAdCAM-1 located on endothelial cells regulates this trafficking. Experimentally, parenteral nutrition (PN) decreases GALT cell mass and mucosal immunity when compared with enteral feeding.


METHODS
In experiment 1, MAdCAM-1 expression was quantified in 32 mice after 4 days of feeding chow, a complex diet, intragastric (IG)-PN, or PN. In experiment 2, MAdCAM-1 was measured in 102 mice 0, 4, 8, 12, 24, 48, or 72 hours after starting PN and at 0, 4, 8, 12, 24, or 48 hours after reinstituting chow following 5 days of PN. In experiment 3, 56 mice received chow, PN, chow + MECA-367 (anti-MAdCAM-1 mAb), or chow + Isotype control Ab (IsoAb) for 5 days, followed by Peyer's patches, lamina propria, and intraepithelial lymphocyte yield with respiratory and intestinal IgA levels. In experiment 4, 10 days after Pseudomonas immunization, mice received chow + MECA-367 or chow + IsoAb for 4 days followed by 1.2 x 108 Pseudomonas intratracheally.


RESULTS
Diet and route affect MAdCAM-1 expression (chow > complex diet > IG-PN > PN). Decreased MAdCAM-1 expression occurred within hours of starting PN in Peyer's patches, but not mesenteric lymph nodes or the intestine, and recovered quickly with enteral refeeding. MAdCAM-1 blockade reduced all GALT populations. Blockade had little effect on IgA levels and partially impaired the late response of established respiratory immunity.


CONCLUSIONS
Enteral feeding affects MAdCAM-1 expression. Complete MAdCAM-1 blockade reduces GALT lymphocytes to PN levels, but the chow feeding stimulus preserves IgA and early antibacterial resistance, implying the existence of non-MAdCAM-1 mechanisms to preserve mucosal immunity.
Ikeda
Shigeo
S
Department of Surgery, The University of Wisconsin-Madison, 600 Highland Avenue, Madison, WI 53792-7375, USA.
Kudsk
Kenneth A
KA
Fukatsu
Kazuhiko
K
Johnson
Cheryl D
CD
Le
Tho
T
Reese
Shannon
S
Zarzaur
Ben L
BL
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D015815:Cell Adhesion Molecules; D004750:Enteral Nutrition; D018928:Immunity, Mucosal / Q000276:immunology*; D007070:Immunoglobulin A / Q000276:immunology; D007136:Immunoglobulins / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D007421:Intestine, Small; D008214:Lymphocytes / Q000276:immunology* / Q000502:physiology; D008221:Lymphoid Tissue / Q000276:immunology*; D008565:Membrane Proteins; D051379:Mice; D009088:Mucoproteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D011552:Pseudomonas Infections / Q000276:immunology; D011550:Pseudomonas aeruginosa; D016201:Receptors, Lymphocyte Homing / Q000037:antagonists & inhibitors / Q000276:immunology*
D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D007070:Immunoglobulin A; D007136:Immunoglobulins; C069886:L-selectin counter-receptors; C489082:Madcam1 protein, mouse; D008565:Membrane Proteins; D009088:Mucoproteins; D016201:Receptors, Lymphocyte Homing