Mononuclear Phagocytic Cells in Human Milk: HLA-DR and FcγR Ligand Expression

Abstract

The study of the cellular immune components of human milk is essential in the understanding of the role human milk may play in protecting the nursing infant against infection. We have investigated some phenotypic characteristics of breast milk macrophages (BMM) and have compared them to the characteristics of adult peripheral blood monocytes (PBM) by using dual parameter flow microfluorometry. Most BMM expressed the monocyte/macrophage markers Leu-M3 and Leu-M5. The latter marker was present in high density (bright) on BMM, but the density of expression of Leu-M3 was higher on PBM than on BMM [median fluorescence intensity (MFI) 409 ± 105 versus 203 ± 106, p = 0.02]. The percentage of BMM (98 ± 2) that expressed the HLA-DR antigen did not differ significantly from PBM, but the density of expression was higher on BMM (MFI 318 ± 56 versus 264 ± 41, p = 0.03). The HLA-DR expression of BMM was further enhanced after incubation with interferon-γ for 36 h; however, receptor for interleukin-2 could not be induced on BMM by this treatment. The expression of the three classes of FcγR was lower on BMM than on PBM, in percentage (FcγRI 56 ± 23 versus 79 ± 17%, p = 0.02), density of expression (FcγRIII MFI 71 ± 20 versus 153 ± 73, p = 0.002), or both (FcγRII 74 ± 22% versus 94 ± 12%, p = 0.02, and MFI 115 ± 53 versus 202 ± 59, p = 0.003). These findings help to define the BMM as a Leu-M3+ (dull), HLA-DR ± (bright), phenotypically mature macrophage with a specifically low expression of the FcγR ligands. These cell surface characteristics could be ontogenic in nature, or could reflect pregnancy-induced down-regulation of the maternal immune system.

Current evidence on the associations of breastfeeding, infant formula, and cow's milk introduction with type 1 diabetes mellitus: a systematic review

“…Additionally, secretory immunoglobin A provides protection against several bacteria such as Escherichia coli , Vibrio cholerae , Streptococcus pneumoniae , Clostridium difficile , Salmonella , and against numerous other viruses 43 . Breast milk also provides infants with macrophages that affect the function of T and B cells, demonstrate phagocytic activity, and secrete immunoregulatory factors 44 …”

Soluble CD30 Antigen in Human Colostrum

“…The main cellular component in mammary secretions is represented by cells whose phe notypic characteristics resemble those of tis sue macrophages rather than monocytes [19], Other milk mononuclear cell types are activated/memory lymphocytes of both the CD4+ and CD8+ T-cell lineage [7,8], These cells elaborate both in vivo and in vitro a vast array of mono-lymphokines, including inter feron-y [9][10][11][12][13][14][15], chronologically the first immunomodulator revealed in human colos trum [20], Interestingly, preliminary results from our laboratories suggest that IL-12, a lymphokine inducing CD30+ cells [17], should be included in the milk cytokine-pro ducing mononuclear cell pool (unpublished data).…”

Immune Protection of Human Milk

“…However, they appear more similar in their phenotypic characteristics to tissue macrophages than to monocytes [44]. Milk macrophages also express major histocompatibility complex class II antigens, and the majority of them express HLA-DR, the intensity of expression of which, is higher than that found in the peripheral blood monocytes but similar to that described in tissue macrophages [44]. After incubation with gamma interferon, their HLA-DR expression was found to be enhanced.…”

“…Furthermore, receptors for lactoferrin [45] and pIgA [46] were detected in human milk macrophages. Finally, they were found to express Fc and C 3 b 3 receptors, but the expression of the three classes of FcÁR was found to be lower than on peripheral blood monocytes [44]. The presence of steroids in human milk could be the reason for it.…”