ELR+ CXC chemokines in human milk.
CXC chemokines bearing the glutamic acid-leucine-arginine (ELR) motif are crucial mediators in neutrophil-dependent acute inflammation. Interestingly, however, Interleukin (IL)-8/CXC ligand (CXCL) 8 is expressed in human milk in biologically significant concentrations, and may play a local maturational role in the developing human intestine. In this chemokine subfamily, there are six other known peptides beside IL-8/CXCL8, all sharing similar effects on neutrophil chemotaxis and angiogenesis. In this study, we measured the concentrations of these chemokines in human milk, sought their presence in human mammary tissue by immunohistochemistry, and confirmed chemokine expression in cultured human mammary epithelial cells (HMECs). Each of the seven ELR(+) CXC chemokines was measurable in milk, and except for NAP-2/CXCL7, these concentrations were higher than serum. The concentrations were higher in colostrum (except for GRO-beta/CXCL2 and NAP-2/CXCL7), and correlated negatively with time elapsed postpartum. IL-8/CXCL8, GRO-gamma/CXCL3, and ENA-78/CXCL5 concentrations were higher in preterm milk. There was intense immunoreactivity in mammary epithelial cells for all ELR(+) CXC chemokines, and the intensity of staining was higher in breast tissue with lactational changes. The supernatants from confluent HMEC cultures also contained measurable concentrations of all the seven ELR(+) CXC chemokines. These results confirm that all ELR(+) CXC chemokines are actively secreted by the mammary epithelial cells into human milk. Further studies are needed to determine if these chemokines share with IL-8/CXCL8 the protective effects on intestinal epithelial cells.
Division of Neonatology, Department of Pediatrics, University of South Florida College of Medicine and All Children's Hospital, Saint Petersburg, FL, USA. amaheshw@hsc.usf.edu
Akhil
A
Maheshwari
Robert D
RD
Christensen
Darlene A
DA
Calhoun
D020816:Amino Acid Motifs; D002478:Cells, Cultured; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D054427:Chemokine CXCL6; D019743:Chemokines, CXC / Q000378:metabolism / Q000502:physiology*; D003470:Culture Media; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D016209:Interleukin-8 / Q000031:analogs & derivatives / Q000378:metabolism; D042361:Mammary Glands, Human / Q000166:cytology / Q000378:metabolism*; D008895:Milk, Human / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D001620:beta-Thromboglobulin
C475829:CXCL1 protein, human; C499707:CXCL3 protein, human; C486263:CXCL5 protein, human; C515503:CXCL6 protein, human; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; D003470:Culture Media; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; C061615:PPBP protein, human; D010455:Peptides; D001620:beta-Thromboglobulin