Macrophages

Macrophages

Macrophages, immune cells of the innate immune system, are important throughout pregnancy. They are well known for their role as antigen presenting cells. But depending on the signals macrophages receive from their environment, they are able to adapt various other functions (e.g. induce tissue repair or regulate immune responses) and even change functions if necessary1.

To exert these different functions, macrophages exist in a spectrum of subtypes. In principle, you can distinguish three types of macrophages: M1 macrophages (classically activated), M2 macrophages (alternatively activated) and, M2-like macrophages/M2c (regulatory macrophage)*. M1 macrophages are typically involved in inflammation and tissue damage and are characterized by the expression of MHCII and cytokines like IFNγ and TNFα. M2 macrophages exert immunosuppressive actions and are characterized by the expression of CD206 and arginase-1. M2-like macrophages are involved in tissue repair mechanisms but also highly associated with fibrosis. M2 and M2-like macrophages share many markers. Currently, IL-10 is the only reliable marker known to distinguish between M2 and M2-like macrophages2.

At the maternal-fetal interface, decidual macrophages are, together with NK cells, the most prominent immune cells during early pregnancy3. They do not belong to either of the above mentioned subtypes, but seem to express a characteristic phenotype. The decidual macrophage phenotype resembles the M2-like macrophages4-6 (see below in the table), but does exert a different expression profile: CD209+, CD163high, CD206+ (mannose receptor), CD304+ (NRP-1), ICAM-3+, CD11clow. They induce maternal-fetal tolerance and placental development by expressing high phagocytic activity, stimulating angiogenesis and, inducing vascular remodeling3. The balance between M1/M2 macrophages is often used as a measure for pregnancy outcome or pregnancy related disorders5, 7, for example miscarriages8.

Monocytes are important precursor cells of tissue macrophages. They circulate in the bloodstream, ready to act upon danger signals and penetrate damaged tissues. Three monocyte subpopulations can be distinguished based on their expression pattern of CD14 and CD16; classical monocyte CD14highCD16neg, non-classical monocyte (CD14dimCD16pos) and the intermediate monocyte (CD14highCD16pos). In pregnancy, changes in monocyte subsets are associated with pre-eclampsia and intrauterine fetal growth restriction9, 10.

The most important markers, cytokines and stimulants to identify and stimulate macrophages are listed below. Are you interested in other markers, different fluorochromes or need help creating a panel for your research purpose? Contact us at techsupport@iqproducts.nl.

*Macrophage nomenclature has been debated for years11. Here we mention the most common names for each subtype

 

Human macrophage markers          
Item Clone Pure FITC R-PE CyQ APC PerCP
CD64 22 IQP-568P IQP-568F IQP-568R IQP-568C IQP-568A
CD64 32.2 IQP-569P IQP-569F IQP-569R
CD68 Y1/82A IQP-641P IQP-641R
CD163 MAC2-158 IQP-570P IQP-570F IQP-570R
CD11c B-ly6 IQP-119P IQP-119R
M1 macrophage markers and cytokines
Item Clone Pure FITC R-PE CyQ APC PerCP
CD86 BU63 IQP-128P IQP-128F
TNF-alpha B-C7 IQP-163P IQP-163R
IL-1beta B-A15 IQP-167P IQP-167R
IL-6 B-E8 IQP-164P IQP-164R
IL-12 B-P24 IQP-168P IQP-168R
M2 macrophage markers and cytokines
Item Clone Pure FITC R-PE CyQ APC PerCP
CD206 15-2 IQP-649P IQP-649R
IL-4 8F-12 IQP-162P IQP-162R
IL-13 B-B13 IQP-166P IQP-166R
M2-like macrophage markers
Item Clone Pure FITC R-PE CyQ APC PerCP
IL-10 B-S10 IQP-175P IQP-175F IQP-175R
Decidual macrophage markers
Item Clone Pure FITC R-PE CyQ APC PerCP
CD14 UCHM1 IQP-143P IQP-143F IQP-143R IQP-143A
CD206 15-2 IQP-649P IQP-649R
CD209 (DC-SIGN) UW60.1 IQP-650P IQP-650R IQP-650A
CD50 (ICAM-3) MEM-171 IQP-640P IQP-640R

 

Monocyte cell markers
Item Clone Pure FITC R-PE CyQ APC PerCP
CD14 UCHM1 IQP-143P IQP-143F IQP-143R IQP-143A
CD16 B-E16 IQP-130P IQP-130F IQP-130R
Anti-HLA-DR BRA30 IQP-134P IQP-134F IQP-134R IQP-134C
Anti-HLA-DR MEM-12 IQP-550P IQP-550F IQP-550R IQP-550A IQP-550PC

 

Cytokines
Item Clone Pure FITC R-PE CyQ APC
IFN-gamma 45-14 IQP-160P IQP-160F IQP-160R IQP-160A
IL-1beta B-A15 IQP-167P IQP-167R
IL-2 N7-48A IQP-161P IQP-161R
IL-4 8F-12 IQP-162P IQP-162R
IL-6 B-E8 IQP-164P IQP-164R
IL-10 B-S10 IQP-175P IQP-175F IQP-175R
IL-12 B-P24 IQP-168P IQP-168R
IL-13 B-B13 IQP-166P IQP-166R
TGF-beta TB21 IQP-169P IQP-169R
TNF-alpha B-C7 IQP-163P IQP-163R

References

 

  • Gordon S., et al. Monocyte and macrophage heterogeneity. Nature Rev. Immunol, 5:953-964, (2005).
  • Mosser D.M., et al. Exploring the full spectrum of macrophage activation. Nature Rev. Immunol, 8:958-969, (2008).
  • Faas M.M., et al. Uterine NK cells and macrophages in pregnancy. Placenta, 56:44-52, (2017)
  • Erlebacher A. Immunology of the maternal-fetal interface. Ann. Rev. Immunol. 31:387-411, (2013)
  • Zhang Y.H., et al. Modulators of the balance between M1 and M2 macrophages during pregnancy. Front. Immunol. 8:120, (2017)
  • Svensson J., et al. Macrophages at the fetal-maternal interface express markers of alternative activation and are induced by M-CSF and IL-10. J. Immunol. 187:3671-3682, (2011)
  • Brown M.B., et al. M1/M2 macrophages polarity in normal and complicated pregnancy. Front. Immunol. 5:606, (2014)
  • Shimada S., et al. Decidual CD68+HLA-DR+CD163 M1 macrophages increase in miscarriages with normal fetal chromosome. Am. J. Reprod. Immunol. 79:e12791, (2018)
  • Faas M.M., et al. Monocytes and macrophages in pregnancy and pre-eclampsia. Front. Immunol. 5:298, (2014)
  • Alahakoon T.I., et al. Distribution of monocyte subsets and polarization in preeclampsia and intrauterine fetal growth restriction. J. Obstet. Gynaecol. Res. 29, (2018)
  • Murray P.J., et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 41(1):14-20, (2014)

 

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