The Role of Zinc and Zinc Homeostasis in Macrophage Function

Table 1

Summary of the immune cell expression and infection-related findings of SLC30 and SLC39 transporters based on previous literature.

(a)

Importer proteins	Expression in macrophages	Expression in other immune cells	Infection-related findings
Slc39a1	Strong expression in the plasma membrane and cytoplasm in THP1-derived macrophages [44]	Expressed in murine T cells [114]	HIV-1 stimulated Slc39a1 expression in alveolar macrophages [115]
Slc39a2	THP1 macrophages: weak expression mainly in nucleoli; TPEN significantly increases Slc39a2 expression; Alveolar macrophages: strong expression in the plasma membrane and cytoplasm [44]	No expression in human monocytes or in granulocytes [46]; moderated expression in murine DCs [116]	Unknown
Slc39a3	Strong expression in human monocytes [46]	Expressed in human T cells and granulocytes [46]	Unknown
Slc39a4	Expressed in alveolar macrophages [117]	Uniform expression in human monocytes and in granulocytes [46]	Chronic alcohol exposure decreases Slc39a4 expression in alveolar macrophages [117]
Slc39a5	Unknown	No expression in human monocytes or in granulocytes [46]	Unknown
Slc39a6	Strong expression in murine macrophages [22]	Expressed in human DCs and T cells [20]	LPS decreases the expression of Slc39a6 in human DCs; Slc39a6-silenced macrophages have increased TNFα expression following LPS stimulation [20]
Slc39a7	Strong expression in murine macrophages [22], which can be inhibited by TPEN [45]	Expressed in murine T cells [114]	Unknown
Slc39a8	Strong expression in both human and murine macrophages	Strong expression in human T cells [21]	Both TNFα and LPS upregulate Slc39a8 expression in human macrophages, which increases zinc uptake and directly inhibits IKKβ [41] and IL-10 [42]
Slc39a9	Unknown	Expressed in murine T cells [114]	Unknown
Slc39a10	Strong expression in murine macrophages	Expressed in murine early B cells [23] and T cells [114]	Slc39a10^fl/fl; LysMCre+ mice have significantly decreased LPS-induced mortality due to increased macrophage apoptosis mediated by zinc-p53 signaling [22]
Slc39a11	Unknown	Expressed in murine T cells [114]	Unknown
Slc39a12	Unknown	Expressed in murine T cells, expression is increased by zinc deficiency [114]	Unknown
Slc39a13	Unknown	Unknown	Unknown
Slc39a14	Expressed in alveolar macrophages, expression is decreased by TPEN [44]	Expressed in leukocytes; Slc39a14-knockout mice have delayed leukocytosis [118]	LPS upregulates Slc39a14 expression and downregulates NF-κB in human macrophages [38]; Slc39a14-knockout mice have impaired zinc uptake and decreased plasma zinc and IL-6 levels following LPS stimulation [119]

(b)

Exporter proteins	Expression in macrophages	Expression in other immune cells	Infection-related findings
Slc30a1	Expressed in alveolar macrophages, expression is decreased by TPEN [44]	Expressed in murine DCs, expression is upregulated by LPS [18]	M. tuberculosis infection upregulates Slc30a1 expression in human macrophages [111]
Slc30a2	Weak expression in macrophages in the nulliparous mammary gland [47]; increased expression in murine macrophages during infection [39]	No expression in human monocytes or granulocytes [46]	Unknown
Slc30a3	Expressed in alveolar macrophages, expression is decreased by TPEN [44]	Expressed at low levels in human peripheral blood lymphocytes [48]	Unknown
Slc30a4	Unknown	Expressed in murine DCs, expression is upregulated by LPS [18]; highly expressed in the human Molt-4 T cell line [48]	GM-CSF upregulate Slc30a4 expression to transport zinc into Golgi [39]
Slc30a5	Expressed in alveolar macrophages, expression is decreased by TPEN [44]	Expressed in murine mast cells and required for the mast cell-mediated delayed-type allergic response [19]	Unknown
Slc30a6	Expressed in THP-1 monocytes, expression is upregulated by zinc deficiency [48]	Expressed in murine DCs, expression is upregulated by LPS [18]	Unknown
Slc30a7	Expressed in THP-2 monocyte, expression is upregulated by zinc deficiency [48]	Expressed in human B lymphocytes with the target molecule CD40 [120]	GM-CSF upregulates Slc30a7 expression, leading to increased zinc transport into the Golgi apparatus [39]
Slc30a8	Unknown	Expressed in human peripheral blood lymphocytes [48]	May function as an autoantigen targeted by disease-associated autoreactive T cells in humans [121]
Slc30a9	Strong expression in murine macrophages [22]	Expressed at low levels in human circulating blood lymphocytes [48]; expressed in murine T cells, expression is decreased by zinc deficiency [114]	Unknown
Slc30a10	Unknown	Unknown	Unknown

DCs: dendritic cells; GM-CSF: granulocyte-macrophage colony-stimulating factor; IL: interleukin; LPS: lipopolysaccharides; TPEN: N,N,N,N-tetrakis(2-pyridylmethyl)-ethylenediamine (a membrane-permeable zinc chelator).