Table 3.
Macrophage defects in mouse models of STIM and ORAI deficiency
| Mouse Macrophages |
In Vitro |
In Vivo |
||||||
|---|---|---|---|---|---|---|---|---|
| Gene | Mouse model | Ca2+ signaling | Chemotaxis | Phagocytosis | Cytokine production | Macrophage function | Pathology | Ref. No. |
| Stim1 | Stim1−/− bone marrow chimera | Decreased SOCE and store content (Tg, PM) | Decreased (C5a) | Reduced phagocytosis (Kupfer cells) | Protected from AIHA, ITP, and pneumonitis | 13 | ||
| Stim1−/− bone marrow chimera | Decreased (Tg, FcγRIII and RIV, PM) | Normal (C5a, CCL2) | Decreased (PM, opsonized RBC) | Normal (TNF and IL-6 in response to LPS) | Normal cytokine secretion (ip LPS injection). Normal macrophage recruitment (Thy peritonitis) | Reduced IgG-induced hemolytic anemia | 108 | |
| Stim1 and Stim2 | Mx1-Cre or Vav-Cre Stim1−/−; Stim2−/− myeloid ablation | Decreased SOCE, normal store content (Tg, BMDM) | Normal (BMDM & PM) IgG-mediated. Normal phago-lysosome fusion | Normal (IL-2, IL-6, IL-10, IL-12p40, IL-12p70, IL-23p19, TNF-α in response to LPS, curdlan, BCG), IL-1b in response to ATP, MSU, FlaTox | 117 | |||
| Stim2 | Global Stim2−/− and Stim2−/− chimera | Decreased SOCE and store content (Tg) Decreased (FcγR) | Decreased (C5a, CCL2) | Decreased 20% (PM, opsonized RBC) | Decreased (TNF and IL-6 in response to LPS) | Reduced cytokine TFN, IL-6, IL-1β secretion (ip LPS injection). Reduced macrophage recruitment (Thy peritonitis) | Increased survival following LPS injection | 108 |
| Orai1 | Orai1−/− chimera | Decreased (Tg, PM) | Normal (C5a, CCL2) | Normal macrophage recruitment (Thy peritonitis) | 109 | |||
The table lists the macrophage defects reported in mouse models of Stim1, Stim2, and Orai1 deficiency. Vav-Cre, knock-in allele with Cre recombinase under control of murine Vav gene regulatory elements; BMDM, bone-marrow derived macrophage; PM, peritoneal macrophages; AIHA, autoimmune hemolytic anemia; ITP, idiopathic thrombocytopenia purpura; SOCE, store-operated Ca2+ entry; BMDM, bone marrow-derived macrophage; RBC, red blood cell; BCG, Bacille Calmette-Guerin; MSU, monosodium urate; ip, intraperitoneal.