Epithelial cells in fetal intestine produce chemerin to recruit macrophages.
Macrophages are first seen in the fetal intestine at 11-12 wk and rapidly increase in number during the 12- to 22-wk period of gestation. The development of macrophage populations in the fetal intestine precedes the appearance of lymphocytes and neutrophils and does not require the presence of dietary or microbial antigens. In this study, we investigated the role of chemerin, a recently discovered, relatively selective chemoattractant for macrophages, in the recruitment of macrophage precursors to the fetal intestine. Chemerin mRNA/protein expression was measured in jejunoileal tissue from 10- to 24-wk human fetuses, neonates operated for intestinal obstruction, and adults undergoing bariatric surgery. The expression of chemerin in intestinal epithelial cells (IECs) was confirmed by using cultured primary IECs and IEC-like cell lines in vitro. The regulatory mechanisms involved in chemerin expression were investigated by in silico and immunolocalization techniques. IECs in the fetal, but not mature, intestine express chemerin. Chemerin expression peaked in the fetal intestine at 20-24 wk and then decreased to original low levels by full term. During the 10- to 24-wk period, chemerin accounted for most of the macrophage chemotactic activity of cultured fetal IECs. The maturational changes in chemerin expression correlated with the expression of retinoic acid receptor-beta in the intestine. Chemerin is an important mediator of epithelial-macrophage cross talk in the fetal/premature, but not in the mature, intestine. Understanding the regulation of the gut macrophage pool is an important step in development of novel strategies to boost mucosal immunity in premature infants and other patient populations at risk of microbial translocation.
Maheshwari
Akhil
A
Pediatrics/Neonatology, Univ. of Alabama at Birmingham, VH648C, 1670 Univ. Blvd., Birmingham, AL 35294, USA. akhil@peds.uab.edu
Kurundkar
Ashish R
AR
Shaik
Sadiq S
SS
Kelly
David R
DR
Hartman
Yolanda
Y
Zhang
Wei
W
Dimmitt
Reed
R
Saeed
Shehzad
S
Randolph
David A
DA
Aprahamian
Charles
C
Datta
Geeta
G
Ohls
Robin K
RK
D000328:Adult; D000595:Amino Acid Sequence; D018938:Caco-2 Cells; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis; D017077:Culture Media, Conditioned / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology*; D005333:Fetus / Q000276:immunology; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006801:Humans; D007082:Ileum / Q000196:embryology / Q000276:immunology*; D007150:Immunohistochemistry; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins; D007583:Jejunum / Q000196:embryology / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018925:Chemokines; D017077:Culture Media, Conditioned; D036341:Intercellular Signaling Peptides and Proteins; C478630:RARRES2 protein, human; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta