Microarray analysis of human milk cells: persistent high expression of osteopontin during the lactation period

Clinical and Experimental Immunology - Tập 138 Số 1 - Trang 47-53 - 2004
T. Nagatomo1, Shouichi Ohga1, Hidetoshi Takada1, A Nomura1, Shunji Hikino1, Mitsuo Imura2, Koichi Ohshima3, Toshiro Hara1
1Department of Paediatrics, Graduate School of Medical Sciences, Kyushu University
2Department of Gynaecology and Obstetrics, Fukuoka City Hospital
3The First Department of Pathology, School of Medicine, Fukuoka University, Fukuoka, Japan

Tóm tắt

SUMMARYTo continue the search for immunological roles of breast milk, cDNA microarray analysis on cytokines and growth factors was performed for human milk cells. Among the 240 cytokine-related genes, osteopontin (OPN) gene ranked top of the expression. Real-time PCR revealed that the OPN mRNA levels in colostrum cells were approximately 100 times higher than those in PHA-stimulated peripheral blood mononuclear cells (PBMNCs), and 10 000 times higher than those in PB CD14+ cells. The median levels of OPN mRNA in early milk or mature milk cells were more than three times higher than those in colostrum cells. Western blot analysis of human milk showed appreciable expression of full-length and short form proteins of OPN. The concentrations of full-length OPN in early milk or mature milk whey continued to be higher than those in colostrum whey and plasma as assessed by ELISA. The early milk (3–7 days postpartum) contained the highest concentrations of OPN protein, while the late mature milk cells (1 years postpartum) had the highest expression of OPN mRNA of all the lactating periods. The results of immunohistochemical and immunocytochemical staining indicated that OPN-producing epithelial cells and macrophages are found in actively lactating mammary glands. These results suggest that the persistently and extraordinarily high expression of OPN in human milk cells plays a potential role in the immunological development of breast-fed infants.

Từ khóa


Tài liệu tham khảo

Hamosh, 2001, Bioactive factors in human milk, Pediatr Clin North Am, 48, 69, 10.1016/S0031-3955(05)70286-8

Soder, 1987, Isolation of interleukin-1 from human milk, Int Arch Allergy Appl Immunol, 83, 19, 10.1159/000234325

Saito, 1991, Detection of IL-6 in human milk and its involvement in IgA production, J Reprod Immunol, 20, 267, 10.1016/0165-0378(91)90051-Q

Palkowetz, 1994, Production of interleukin-6 and interleukin-8 by human mammary gland epithelial cells, J Reprod Immunol, 26, 57, 10.1016/0165-0378(93)00867-S

Bryan, 1999, Interleukin-12 in human milk, Pediatr Res, 45, 858, 10.1203/00006450-199906000-00013

Takahata, 2001, Interleukin-18 in human milk, Pediatr Res, 50, 268, 10.1203/00006450-200108000-00017

Rudloff, 1992, Tumor necrosis factor-alpha in human milk, Pediatr Res, 31, 29, 10.1203/00006450-199201000-00005

Eglinton, 1994, Phenotype of T cells, their soluble receptor levels, and cytokine profile of human breast milk, Immunol Cell Biol, 72, 306, 10.1038/icb.1994.46

Srivastava, 1996, Cytokines in human milk, Res Commun Mol Pathol Pharmacol, 93, 263

Hara, 1995, Identification of macrophage colony-stimulating factor in human milk and mammary gland epithelial cells, Pediatr Res, 37, 437, 10.1203/00006450-199504000-00009

Calhoun, 2000, Granulocyte colony-stimulating factor is present in human milk and its receptor is present in human fetal intestine, Pediatrics, 105, e7, 10.1542/peds.105.1.e7

Siafakas, 1999, Vascular endothelial growth factor (VEGF) is present in human breast milk and its receptor is present on intestinal epithelial cells, Pediatr Res, 45, 652, 10.1203/00006450-199905010-00007

Xanthou, 1995, Human milk and intestinal host defense in newborns: an update, Adv Pediatr, 42, 171, 10.1016/S0065-3101(24)00115-4

Bernt, 1999, Human milk as a carrier of biochemical messages, Acta Paediatr Suppl, 88, 27, 10.1111/j.1651-2227.1999.tb01298.x

Ashkar, 2000, Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity, Science, 287, 860, 10.1126/science.287.5454.860

O'Regan, 1999, Osteopontin is associated with T cells in sarcoid granulomas and has T cell adhesive and cytokine-like properties in vitro, J Immunol, 162, 1024, 10.4049/jimmunol.162.2.1024

Giachelli, 1998, Evidence for a role of osteopontin in macrophage infiltration in response to pathological stimuli in vivo, Am J Pathol, 152, 353

Hwang, 1994, Osteopontin inhibits induction of nitric oxide synthase gene expression by inflammatory mediators in mouse kidney epithelial cells, J Biol Chem, 269, 711, 10.1016/S0021-9258(17)42407-0

Senger, 1989, Purification of a human milk protein closely similar to tumor-secreted phosphoproteins and osteopontin, Biochim Biophys Acta, 996, 43, 10.1016/0167-4838(89)90092-7

Dhanireddy, 1993, Osteopontin in human milk from mothers of premature infants, Acta Paediatr, 82, 821, 10.1111/j.1651-2227.1993.tb17619.x

Repnik, 2003, Simple and cost-effective isolation of monocytes from buffy coats, J Immunol Meth, 278, 283, 10.1016/S0022-1759(03)00231-X

Shibakura, 2003, Induction of IL-8 and monoclyte chemoattractant protein-1 by doxorubicin in human small cell lung carcinoma cells, Int J Cancer, 103, 380, 10.1002/ijc.10842

Hattori, 2001, High expression of platelet-derived growth factor and transforming growth factor-beta 1 in blast cells from patients with Down Syndrome suffering from transient myeloproliferative disorder and organ fibrosis, Br J Haematol, 115, 472, 10.1046/j.1365-2141.2001.03093.x

Hirata, 2002, ZD1839 (Iressa) induces antiangiogenic effects through inhibition of epidermal growth factor receptor tyrosine kinase, Cancer Res, 62, 2554

Rudloff, 1999, Inflammation markers and cytokines in breast milk of atopic and nonatopic women, Allergy, 54, 206, 10.1034/j.1398-9995.1999.00765.x

Bottcher, 2000, Chemoattractant factors in breast milk from allergic and nonallergic mothers, Pediatr Res, 47, 592, 10.1203/00006450-200005000-00006

Picciano, 2001, Nutrient composition of human milk, Pediatr Clin North Am, 48, 53, 10.1016/S0031-3955(05)70285-6

Xanthou, 1997, Human milk cells, Acta Paediatr, 86, 1288, 10.1111/j.1651-2227.1997.tb14899.x

Rickard, 2003, Phytoestrogen genistein acts as an estrogen agonist on human osteoblastic cells through estrogen receptors alpha and beta, J Cell Biochem, 89, 633, 10.1002/jcb.10539

Nemir, 2000, Targeted inhibition of osteopontin expression in the mammary gland causes abnormal morphogenesis and lactation deficiency, J Biol Chem, 275, 969, 10.1074/jbc.275.2.969

Nau, 1999, Attenuated host resistance against Mycobacterium bovis BCG infection in mice lacking osteopontin, Infect Immun, 67, 4223, 10.1128/IAI.67.8.4223-4230.1999

Nau, 2000, Osteopontin expression correlates with clinical outcome in patients with mycobacterial infection, Am J Pathol, 157, 37, 10.1016/S0002-9440(10)64514-2

Pabst, 1989, Effect of breast-feeding on immune response to BCG vaccination, Lancet, 1, 295, 10.1016/S0140-6736(89)91307-X

Pabst, 1997, Differential modulation of the immune response by breast- or formula-feeding of infants, Acta Paediatr, 86, 1291, 10.1111/j.1651-2227.1997.tb14900.x

Rittling, 1999, Osteopontin function in pathology: lessons from osteopontin-deficient mice, Exp Nephrol, 7, 103, 10.1159/000020591

Mastretta, 2002, Effect of Lactobacillus GG and breast-feeding in the prevention of rotavirus nosocomial infection, J Pediatr Gastroenterol Nutr, 35, 527, 10.1097/00005176-200210000-00013

Naficy, 1999, Epidemiology of rotavirus diarrhea in Egyptian children and implications for disease control, Am J Epidemiol, 150, 770, 10.1093/oxfordjournals.aje.a010080

Belin, 1993, Involvement of cellular adhesion sequences in the attachment of adenovirus to the HeLa cell surface, J General Virol, 74, 1485, 10.1099/0022-1317-74-8-1485

Strachan, 1995, Breastfeeding as prophylaxis against atopic disease, [Comment] Lancet, 346, 1714, 10.1016/S0140-6736(95)92884-7

Sepp, 1997, Intestinal microflora of Estonian and Swedish infants, Acta Paediatr, 86, 956, 10.1111/j.1651-2227.1997.tb15178.x

Oldberg, 1986, Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence, Proc Natl Acad Sci USA, 83, 8819, 10.1073/pnas.83.23.8819

Yoshitake, 1999, Osteopontin-deficient mice are resistant to ovariectomy-induced bone resorption, Proc Natl Acad Sci USA, 96, 8156, 10.1073/pnas.96.14.8156

Ihara, 2001, Parathyroid hormone-induced bone resorption does not occur in the absence of osteopontin, J Biol Chem, 276, 13065, 10.1074/jbc.M010938200

Bayless, 1997, Isolation and biological properties of osteopontin from bovine milk, Protein Expr Purif, 9, 309, 10.1006/prep.1996.0699

Thông tin
Thông tin xuất bản

Clinical and Experimental Immunology

Tập 138 Số 1

47-53

Thông tin tác giả