Skip to main content
Log in

Do Inflammatory Cells Participate in Mammary Gland Involution?

  • Published:
Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

The processes by which the involuting mammary gland clears residual milk and milk fat, as well as apoptotic cells, have gone largely unstudied in the modern literature. Here we review the evidence for and against the involvement of professional phagocytes of hematopoetic lineage in this process. Additionally we present evidence that mammary epithelial cells themselves are capable of phagocytosis and may be responsible for the majority of apoptotic cell and residual milk clearance during murine involution. In this scheme these cells regulate their cytokine production in response to apoptotic cells in a manner similar to other cells, including macrophages. The ensuing model describes a process of involution that actively suppresses an inflammatory response in the gland, allowing for effective tissue remodeling and damage prevention.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. L. M. A. Maeder (1922). Changes in the mammary gland of the albino rat (mus norvegicus albinus) during lactation and involution. Am.J.Anat. 31: 1–26.

    Google Scholar 

  2. W. L. Williams (1942). Normal and experimental mammary involution in the mouse as related to the inception and cessa-tion of lactation. Am.J.Anat. 71: 1–41.

    Google Scholar 

  3. S. R. Wellings and K. B. DeOme (1963). Electron microscopy of milk secretion in the mammary gland of the c3h/crgl mouse. III. Cytomorphology of the involuting gland. J.Natl.Cancer Inst. 30: 241–267.

    Google Scholar 

  4. K. K. Sekhri, D. R. Pitelka, and K. B. DeOme (1967). Studies of mouse mammary glands. I. Cytomorphology of the normal mammary gland. J.Natl.Cancer Inst. 39: 459–490.

    Google Scholar 

  5. R. C. Richards and G. K. Benson (1971). Ultrastructural changes accompanying involution of the mammary gland in the albino rat. J.Endocrinol. 51: 127–135.

    Google Scholar 

  6. C. Alexander, S. Selvarajan, J. Mudgett, and Z. Werb (2001). Stromelysin-1 regulates adipogenesis during mammary gland involution. J.Cell Biol. 152: 693–703.

    Google Scholar 

  7. V. Gouon-Evans, M. E. Rothenberg, and J. W. Pollard (2000). Postnatal mammary gland development requires macrophages and eosinophils. Development 127: 2269–2282.

    Google Scholar 

  8. C. Wilde, C. Knight, and D. Flint (1999). Control of milk se-cretion and apoptosis during mammary involution. J.Mam. Gland Biol.Neoplasia 4: 129–136.

    Google Scholar 

  9. M. Paape, K. Shafer-Weaver, A. Capuco, K. Oostveldt, and C. Burvenich (2000). Immune surveillance of mammary tissue by phagocytic cells. Adv.Exp.Med.Biol. 480: 259–277.

    Google Scholar 

  10. C. S. Lee, G. H. McDowell, and A. K. Lascelles (1969). The importance of macrophages in the removal of fat from the involuting mammary gland. Res.Vet.Sci. 10: 34–38.

    Google Scholar 

  11. W. Nordin and C. S. Lee (1982). Cytology of milk in guinea pigs. Acta Anat. 113: 135–144.

    Google Scholar 

  12. C. S. Lee, I. McCauley, and P. E. Hartmann (1983). Light and electron microscopy of cells in pig colostrum, milk and invo-lution secretion. Acta Anat. 116: 126–135.

    Google Scholar 

  13. I. G. Colditz (1988). Studies on the inflammatory response during involution of the ovine mammary gland. Q.J. Exp. Physiol. 73: 363–368.

    Google Scholar 

  14. L. Tatarczuch, C. Philip, and C. S. Lee (2000). Leucocyte phe-notypes in involuting and fully involuted mammary glandular tissues and secretions of sheep. J.Anat. 196: 313–326.

    Google Scholar 

  15. S. Nickerson (1989). Immunological aspects of mammary in-volution. J.Dairy Sci. 72: 1665–1678.

    Google Scholar 

  16. N. Manlongat, T. Yang, L. Hinckley, R. Bendel, and H. Krider (1998). Physiologic-chemoattractant-induced migration of polymorphonuclear leukocytes in milk. Clin.Diagn. Lab.Immunol. 5: 375–381.

    Google Scholar 

  17. M. Limon (1902). Phenomenes histologiques de la secre-tion lactee. Journal de l'anatomie et de la physiologie 38: 14–34.

    Google Scholar 

  18. S. Bratianu and C. Guerriero (1930). Sur le pouvoir phago-cytaire des cellules epitheliales de la glande mammaire. C.R. Hebd.Seanc.Acad.Sci.Paris 190: 1529–1530.

    Google Scholar 

  19. N. I. Walker, R. E. Bennet, and J. F. R. Kerr (1989). Cell death by apoptosis during involution of the lactating breast in mice and rats. Am.J.Anat. 185: 19–32.

    Google Scholar 

  20. H. J. Helminen and J. L. Ericsson (1968). Studies on mammary gland involution: II. Ultrastructural evidence for auto-and heterophagocytosis. J.Ultrastruct.Res. 25: 214–227.

    Google Scholar 

  21. H. J. Helminen and J. L. Ericsson (1971). Effects of enforced milk stasis on mammary gland epithelium, with special ref-erence to changes in lysosomes and lysosomal enzymes. Exp. Cell Res. 68: 411–427.

    Google Scholar 

  22. H. E. Mayberry (1964). Macrophages in post-secretory mam-mary involution in mice. Anat.Rec. 149: 99–112.

    Google Scholar 

  23. R. C. Richards and G. K. Benson (1971). Involvement of the macrophage system in the involution of the mammary gland in the albino rat. J.Endocrinol. 51: 149–156.

    Google Scholar 

  24. L. Tatarczuch, C. Philip, and C. S. Lee (1997). Involution of the sheep mammary gland. J.Anat. 190: 405–416.

    Google Scholar 

  25. J. Savill, V. Fadok, P. Henson, and C. Haslett (1993). Phagocyte recognition of cells undergoing apoptosis. Immunol.Today 14: 131–136.

    Google Scholar 

  26. H. J. Helminen and J. L. Ericsson (1968). Studies on mam-mary gland involution: I. On the ultrastructure of the lactating mammary gland. J.Ultrastruct.Res. 25: 193–213.

    Google Scholar 

  27. G. Chepko and G. H. Smith (1997). Three division-competent, structurally-distinct cell populations contribute to murine mammary epithelial renewal. Tissue Cell 29: 239–253.

    Google Scholar 

  28. G. Chepko and G. H. Smith (1999). Mammary epithelial stem cells: Our current understanding. J.Mammary Gland Biol. Neoplasia 4: 35–52.

    Google Scholar 

  29. G. H. Smith and G. Chepko (2001). Mammary epithelial stem cells. Microsc.Res.Tech. 52: 190–203.

    Google Scholar 

  30. P. Masso-Welch, K. Darcy, N. Stangle-Castor, and M. Ip (2000). A developmental atlas of rat mammmary gland histology. J.Mammary Gland Biol.Neoplasia 5: 165–185.

    Google Scholar 

  31. R. Talhouk, M. Bissell, and Z. Werb (1992). Coordinated expression of extracellular matrix-degrading proteinases and their inhibitors regulates mammary epithelial function during involution. J.Cell Biol. 118: 1271–1282.

    Google Scholar 

  32. L. R. Lund (1996). Two distinct phases of apoptosis in mammary gland involution: Proteinase-independent and dependent pathways. Development 122: 181–193.

    Google Scholar 

  33. M. Li, X. Liu, G. Robinson, U. Bar-Peled, K. U. Wagner, W. S. Young, L. Hennighausen, and P. A. Furth (1997). Mammary-derived signals activate programmed cell death during the first stage of mammary gland involution. Proc.Natl. Acad.Sci.U.S.A. 94: 3425–3430.

    Google Scholar 

  34. R. Kumar, R. K. Vadlamudi, and L. Adam(2000). Apoptosis in mammary gland and cancer. Endocrine-Related Cancer 7: 257–269.

    Google Scholar 

  35. R. Strange, T. Metcalfe, L. Thackray, and M. Dang (2001). Apoptosis in normal and neoplastic mammary gland devel-opment. Microsc.Res.Tech. 52: 171–181.

    Google Scholar 

  36. J. Rosenblatt, M. C. Raff, and L. P. Cramer (2001). An epithe-lial cell destined for apoptosis signals its neighbors to extrude it by an actin-and myosin-dependent mechanism. Curr.Biol. 11: 1847–1857.

    Google Scholar 

  37. K. D. Walton, K. U. Wagner, E. B. Rucker, III, J. M. Shillingford, K. Miyoshi, and L. Hennighausen (2001). Con-ditional deletion of the bcl-x gene from mouse mammary ep-ithelium results in accelerated apoptosis during involution but does not compromise cell function during lactation. Mech. Dev. 109: 281–293.

    Google Scholar 

  38. A. Marti, P. Ritter, R. Jager, H. Lazar, A. Baltzer, J. Schenkel, W. Declercq, P. Vandenabeele, and R. Jaggi (2001). Mouse mammary gland involution is associated with cytochrome c release and caspase activation. Mech.Dev. 104: 89–98.

    Google Scholar 

  39. L. Quarrie, C. Addey, and C. Wilde (1996). Programmed cell death during mammary tissue involution induced by weaning, litter removal, and milk stasis. J.Cell Physiol. 168: 559–569.

    Google Scholar 

  40. J. U. Schweichel and H. J. Merker (1973). The morphology of various types of cell death in prenatal tissues. Teratology 7: 253–266.

    Google Scholar 

  41. L. M. Schwartz, S. W. Smith, M. E. Jones, and B. A. Osborne (1993). Do all programmed cell deaths occur via apoptosis? Proc.Natl.Acad.Sci.U.S.A. 90: 980–984.

    Google Scholar 

  42. D. J. Klionsky and S. D. Emr (2000). Autophagy as a regulated pathway of cellular degradation. Science 290: 1717–1721.

    Google Scholar 

  43. W. Bursch (2001). The autophagosomal-lysosomal compart-ment in programmed cell death. Cell Death Differ. 8: 569–581.

    Google Scholar 

  44. H. J. Helminen and J. L. Ericsson (1968). Studies on mammary gland involution: III. Alterations outside auto-and heterophagocytic pathways for cytoplasmic degradation. J.Ultrastruct.Res. 25: 228–239.

    Google Scholar 

  45. D. Brandes, E. Anton, and S. Barnard (1969). Lysosomes and cellular regressive changes in rat mammary gland involution. Lab.Invest. 20: 465–471.

    Google Scholar 

  46. E. I. Carlsson, B. W. Karlsson, and K. H. C. Waldemarson (1973). Dehydrogenases and nucleic acids in rat mammary gland during involution initiated at various stages of lactation. Comp.Biochem.Physiol.B 44: 93–108.

    Google Scholar 

  47. X. H. Liang, S. Jackson, M. Seaman, K. Brown, B. Kempkes, H. Hibshnoosh, and B. Levine (1999). Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402: 672–676.

    Google Scholar 

  48. S. Paglin, T. Hollister, T. Delohery, N. Hackett, M. McMahill, E. Sphicas, D. Domingo, and J. Yahalom (2001). A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles. Cancer Res. 61: 439–444.

    Google Scholar 

  49. H. J. Helminen, J. L. Ericsson, and S. Orrenius (1968). Studies on mammary gland involution: IV. Histochemical and bio-chemical observations on alterations in lysosomes and lysoso-mal enzymes. J.Ultrastruct.Res. 25: 240–252.

    Google Scholar 

  50. K. U. Wagner, C. Boulanger, M. Henry, M. Sgagias, L. Hennighausen, and G. H. Smith (2002). An adjunct mammary epithelial cell population in parous females: Its role in func-tional adaptation and tissue renewal. Development 129: 1377–1386.

    Google Scholar 

  51. M. Berg, A. Dharmarajan, and B. Waddell (2002). Glucocor-ticoids and progesterone prevent apoptosis in the lactating rat mammary gland. Endocrinology 143: 222–227.

    Google Scholar 

  52. C. D. Gregory (2000). CD14-dependent clearance of apoptotic cells: Relevance to the immune system. Curr.Opin.Immunol. 12: 27–34.

    Google Scholar 

  53. V. A. Fadok, D. L. Bratton, and P. M. Henson (2001). Phago-cyte receptors for apoptotic cells: Recognition, uptake, and consequences. J.Clin.Invest. 108: 957–962.

    Google Scholar 

  54. V. A. Fadok and G. Chimini (2001). The phagocytosis of apop-totic cells. Semin.Immunol. 13: 365–372.

    Google Scholar 

  55. R. A. Schlegel and P. Williamson (2001). Phosphatidylserine, a death knell. Cell Death Differ. 8: 551–563.

    Google Scholar 

  56. F. Geske, J. Monks, L. Lehman, and V. Fadok (2002). The role of the macrophage in apoptosis: Hunter, gatherer and regulator. J.Hematol. 76: 16–26.

    Google Scholar 

  57. J. Savill, N. Hogg, and C. Haslett (1991). Macrophage vit-ronectin receptor, CD36, and thrombospondin cooperate in recognition of neutrophils undergoing programmed cell death. Chest 99: 6S–7S.

    Google Scholar 

  58. F. Takizawa, T. Shoutaro, and S. Nagasawa (1996). Enhance-ment of macrophage phagocytosis upon IC3b deposition on apoptotic cells. FEBS Lett. 397: 269–272.

    Google Scholar 

  59. K. Balasubramanian, J. Chandra, and A. J. Schroit (1997). Immune clearance of phosphatidylserine-expressing cells by phagocytes. The role of beta2-glycoprotein I in macrophage recognition. J.Biol.Chem. 272: 31113–31117.

    Google Scholar 

  60. L. C. Korb and J. M. Ahearn (1997). C1q binds directly and specifically to surface blebs of apoptotic human keratinocytes: Complement deficiency and systemic lupus erythematosus re-visited. J.Immunol. 158: 4525–4528.

    Google Scholar 

  61. M. Botto, C. Dell'Agnola, A. E. Bygrave, E. M. Thompson, H. T. Cook, F. Petry, M. Loos, P. P. Pandolfi, and M. J. Walport (1998). Homozygous C1q deficiency causes glomerulonephri-tis associated with multiple apoptotic bodies [see comments]. Nat.Genet. 19: 56–59.

    Google Scholar 

  62. D. Mevorach, J. O. Mascarenhas, D. Gershov, and K. B. Elkon (1998). Complement-dependent clearance of apoptotic cells by human macrophages. J.Exp.Med. 188: 2313–2320.

    Google Scholar 

  63. D. Gershov, S. Kim, N. Brot, and K. B. Elkon (2000). C-reactive protein binds to apoptotic cells, protects the cells from assembly of the terminal complement components, and sustains an antiinflammatory innate immune response: Im-plications for systemic autoimmunity. J.Exp.Med. 192: 1353–1364.

    Google Scholar 

  64. P. Rovere, G. Peri, F. Fazzini, B. Bottazzi, A. Doni, A. Bondanza, V. S. Zimmermann, C. Garlanda, U. Fascio, M. G. Sabbadini, C. Rugarli, A. Mantovani, and A. A. Manfredi (2000). The long pentraxin ptx3 binds to apoptotic cells and regulates their clearance by antigen-presenting dendritic cells. Blood 96: 4300–4306.

    Google Scholar 

  65. P. R. Taylor, A. Carugati, V. A. Fadok, H. T. Cook, M. Andrews, M. C. Carroll, J. S. Savill, P. M. Henson, M. Botto, and M. J. Walport (2000). A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J Exp.Med. 192: 359–366.

    Google Scholar 

  66. C. A. Ogden, A. deCathelineau, P. R. Hoffmann, D. Bratton, B. Ghebrehiwet, V. A. Fadok, and P. M. Henson (2001). C1q and mannose binding lectin engagement of cell surface cal-reticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells. J.Exp.Med. 194: 781–795.

    Google Scholar 

  67. R. Hanayama, M. Tanaka, K. Miwa, A. Shinohara, A. Iwamatsu, and S. Nagata (2002). Identification of a factor that links apoptotic cells to phagocytes. Nature. 417: 182–187.

    Google Scholar 

  68. A. Moynault, M. F. Luciani, and G. Chimini (1998). ABC1, the mammalian homologue of the engulfment gene ced-7, is required during phagocytosis of both necrotic and apoptotic cells. Biochem.Soc.Trans. 26: 629–635.

    Google Scholar 

  69. Y. Hamon, C. Broccardo, O. Chambenoit, M. F. Luciani, F. Toti, S. Chaslin, J. M. Freyssinet, P. F. Devaux, J. McNeish, D. Marguet, and G. Chimini (2000). ABC1 promotes engulf-ment of apoptotic cells and transbilayer redistribution of phos-phatidylserine. Nat.Cell.Biol. 2: 399–406.

    Google Scholar 

  70. Y. Ishimoto, K. Ohashi, K. Mizuno, and T. Nakano (2000). Promotion of the uptake of PS liposomes and apoptotic cells by a product of growth arrest-specific gene, gas6. J.Biochem. (Tokyo) 127: 411–417.

    Google Scholar 

  71. E. Nandrot, E. M. Dufour, A. C. Provost, M. O. Pequignot, S. Bonnel, K. Gogat, D. Marchant, C. Rouillac, B. Sepulchre de Conde, M. T. Bihoreau, C. Shaver, J. L. Dufier, C. Marsac, M. Lathrop, M. Menasche, and M. M. Abitbol (2000). Ho-mozygous deletion in the coding sequence of the c-mer gene in RCS rats unravels general mechanisms of physiological cell adhesion and apoptosis. Neurobiol.Dis. 7: 586–599.

    Google Scholar 

  72. M. O. Hall, A. L. Prieto, M. S. Obin, T. A. Abrams, B. L. Burgess, M. J. Heeb, and B. J. Agnew (2001). Outer segment phagocytosis by cultured retinal pigment epithelial cells re-quires gas6. Exp.Eye Res. 73: 509–520.

    Google Scholar 

  73. R. S. Scott, E. J. McMahon, S. M. Pop, E. A. Reap, R. Caricchio, P. L. Cohen, H. S. Earp, and G. K. Matsushima (2001). Phagocytosis and clearance of apoptotic cells is medi-ated by mer. Nature 411: 207–211.

    Google Scholar 

  74. E. Duvall, A. H. Wyllie, and R. G. Morris (1985). Macrophage recognition of cells undergoing programmed cell death (apop-tosis). Immunology 56: 351–358.

    Google Scholar 

  75. L. Dini, F. Autuori, A. Lentini, S. Oliverio, and M. Piacentini (1992). The clearance of apoptotic cells in the liver is mediated by the asialoglycoprotein receptor. FEBS Lett. 296: 174–178.

    Google Scholar 

  76. L. Falasca, A. Bergamini, A. Serafino, C. Balabaud, and L. Dini (1996). Human Kupffer cell recognition and phagocyto-sis of apoptotic peripheral blood lymphocytes. Exp.Cell Res. 224: 152–162.

    Google Scholar 

  77. L. Dini and E. C. Carla (1998). Hepatic sinusoidal endothe-lium heterogeneity with respect to the recognition of apoptotic cells. Exp.Cell Res. 240: 388–393.

    Google Scholar 

  78. M. Ruzittu, E. C. Carla, M. R. Montinari, G. Maietta, and L. Dini (1999). Modulation of cell surface expression of liver carbohydrate receptors during in vivo induction of apoptosis with lead nitrate. Cell Tissue Res. 298: 105–112.

    Google Scholar 

  79. C. D. Gregory, A. Devitt, and O. Moffatt (1998). Roles of ICAM-3 and CD14 in the recognition and phagocytosis of apoptotic cells by macrophages. Biochem.Soc.Trans. 26: 644–649.

    Google Scholar 

  80. O. D. Moffatt, A. Devitt, E. D. Bell, D. L. Simmons, and C. D. Gregory (1999). Macrophage recognition of ICAM-3 on apoptotic leukocytes. J.Immunol. 162: 6800–6810.

    Google Scholar 

  81. M. K. Callahan, P. Williamson, and R. A. Schlegel (2000). Surface expression of phosphatidylserine on macrophages is required for phagocytosis of apoptotic thymocytes. Cell Death Differ 7: 645–653.

    Google Scholar 

  82. P. R. Hoffmann, A. M. deCathelineau, C. A. Ogden, Y. Leverrier, D. L. Bratton, D. L. Daleke, A. J. Ridley, V. A. Fadok, and P. M. Henson (2001). Phosphatidylserine (PS) in-duces PS receptor-mediated macropinocytosis and promotes clearance of apoptotic cells. J.Cell Biol. 155: 649–660.

    Google Scholar 

  83. K. Kurosaka, N. Watanabe, and Y. Kobayashi (2001). Pro-duction of proinflammatory cytokines by resident tissue macrophages after phagocytosis of apoptotic cells. Cell Immunol. 211: 1–7.

    Google Scholar 

  84. V. A. Fadok, D. L. Bratton, D. M. Rose, A. Pearson, R. A. Ezekewitz, and P. M. Henson (2000). A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 405: 85–90.

    Google Scholar 

  85. S. E. Hall, J. Savill, J. E. Henson, and C. Haslett (1994). Apop-totic neutrophils are phagocytosed by fibroblasts with partici-pation of the fibroblast vitronectin receptor and involvement of a mannose/fucose-specific lectin. J.Immunol. 153: 3218–3227.

    Google Scholar 

  86. M. R. Bennett, D. F. Gibson, S. M. Schwartz, and J. F. Tait (1995). Binding and phagocytosis of apoptotic vascular smooth muscle cells is mediated in part by exposure of phos-phatidylserine. Circ.Res. 77: 1136–1142.

    Google Scholar 

  87. L. Dini, A. Lentini, G. D. Diez, M. Rocha, L. Falasca, L. Serafino, and F. Vidal-Vanaclocha (1995). Phagocytosis of apoptotic bodies by liver endothelial cells. J.Cell Sci. 108: 967–973.

    Google Scholar 

  88. S. C. Finnemann and E. Rodriguez-Boulan (1999). Macrophage and retinal pigment epithelium phagocy-tosis: Apoptotic cells and photoreceptors compete for alphavbeta3 and alphavbeta5 integrins, and protein kinase c regulates alphavbeta5 binding and cytoskeletal linkage. J.Exp.Med. 190: 861–874.

    Google Scholar 

  89. G. M. Walsh, D. W. Sexton, M. G. Blaylock, and C. M. Convery (1999). Resting and cytokine-stimulated human airway epithelial cells recognize and engulf apoptotic eosinophils. Blood 94: 2827–2835.

    Google Scholar 

  90. V. A. Fadok, A. de Cathelineau, D. L. Daleke, P. M. Henson, and D. L. Bratton (2001). Loss of phospholipid asymmetry and surface exposure of phosphatidylserine is required for phago-cytosis of apoptotic cells by macrophages and fibroblasts. J.Biol.Chem. 276: 1071–1077.

    Google Scholar 

  91. S. C. Finnemann and R. L. Silverstein (2001). Differential roles of CD36 and alphavbeta5 integrin in photoreceptor phagocy-tosis by the retinal pigment epithelium. J.Exp.Med. 194: 1289–1298.

    Google Scholar 

  92. D. W. Sexton, M. G. Blaylock, and G. M. Walsh (2001). Human alveolar epithelial cells engulf apoptotic eosinophils by means of integrin-and phosphatidylserine receptor-dependent mechanisms: A process upregulated by dexam-ethasone. J.Allergy Clin.Immunol. 108: 962–969.

    Google Scholar 

  93. R. Parnaik, M. C. Raff, and J. Scholes (2000). Differences be-tween the clearance of apoptotic cells by professional and non-professional phagocytes. Curr.Biol. 19: 857–860.

    Google Scholar 

  94. W. Wood, M. Turmaine, R. Weber, V. Camp, R. A. Maki, S. R. McKercher, and P. Martin (2000). Mesenchymal cells engulf and clear apoptotic footplate cells in macrophageless PU.1 null mouse embryos. Development 127: 5245–5252.

    Google Scholar 

  95. A. Gorska, J. Derynck, H. Moses, and R. Serra (1998). Dominant-negative interference of the transforming growth factor beta type II receptor in mammary gland epithelium results in alveolar hyperplasia and differentiation in virgin mice. Cell Growth Differ. 9: 229–238.

    Google Scholar 

  96. D. Linzer and S. Fisher (1999). The placenta and the prolactin family of hormones: Regulation of the physiology of preg-nancy. Mol.Endocrinol. 13: 837–840.

    Google Scholar 

  97. D. Grattan (2001). The actions of prolactin in the brain during pregnancy and lactation. Prog.Brain Res. 133: 153–171.

    Google Scholar 

  98. R. P. Garofalo and A. S. Goldman (1998). Cytokines, chemokines and colony-stimulating factors in human milk: The 1997 update. Biol.Neonate 74: 134–142.

    Google Scholar 

  99. J. Fata, K. Leco, E. Voura, H. Yu, P. Waterhouse, G. Murphy, R. Moorehead, and R. Khokha (2001). Accelerated apoptosis in the TIMP-3-deficient mammary gland. J.Clin.Invest. 108: 831–841.

    Google Scholar 

  100. L. R. Lund, S. Bjorn, M. Sternlicht, B. Nielsen, H. Solberg, P. Usher, R. Osterby, I. Christensen, R. Stephens, T. Bugge, K. Dano, and Z. Werb (2000). Lactational competence and involution of the mouse mammarygland require plasminogen. Development 127: 4481–4492.

    Google Scholar 

  101. R. A. Lang and J. M. Bishop (1993). Macrophages are required for cell death and tissue remodeling in the developing mouse eye. Cell 74: 453–462.

    Google Scholar 

  102. M. Schmitt-Ney, B. Happ, P. Hofer, N. E. Hynes, and B. Groner (1992). Mammary gland-specific nuclear factor activity is pos-itively regulated by lactogenic hormones and negatively by milk stasis. Mol.Endocrinol. 6: 1988–1997.

    Google Scholar 

  103. R. Jaggi, A. Marti, K. Guo, Z. Feng, and R. Friis (1996). Reg-ulation of physiological apoptosis: Mouse mammmary invo-lution. J.Dairy Sci. 79: 1074–1084.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Monks, J., Geske, F.J., Lehman, L. et al. Do Inflammatory Cells Participate in Mammary Gland Involution?. J Mammary Gland Biol Neoplasia 7, 163–176 (2002). https://doi.org/10.1023/A:1020351919634

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1020351919634

Navigation