Table 1.
Neutrophil defects in mouse models of STIM and ORAI deficiency
| Mouse Neutrophils |
In Vitro |
In Vivo |
|||||
|---|---|---|---|---|---|---|---|
| Gene | Mouse model | Ca2+ signaling | Adhesion/migration | Phagocytosis/ROS | Neutrophil recruitment | Pathology | Ref. No. |
| Stim1 | Stim1−/− bone marrow chimera | Normal chemotaxis (C5a, MIP-2) | Normal (lung, IgG-IC) | 13 | |||
| LysM-Cre myeloid ablation | Decreased (local Ca2+ signals) | Decreased phagocytosis (opsonized RBC) | 73 | ||||
| Stim1−/− fetal liver chimera | Decreased (fMLP, MIP-2, IC, pRGD) | Normal adhesion (fibrinogen); normal chemotaxis (MIP-2, fMLP) | Decreased phagocytosis (S. aureus); decreased ROS production (fMLP, pRGD, zymosan) | Normal (Thy peritonitis) | Increased bacterial pneumonia & septicemia; decreased liver ischemia-reperfusion injury | 126 | |
| LysM-Cre myeloid ablation | Decreased (Tg) | Reduced chemotaxis (fMIVIL, WKY, KC, MIP-2) | Decreased (skin, IMQ) | Faster recovery of psoriasis-like plaques | 112 | ||
| Stim1−/− bone marrow chimera | Decreased (Tg) Normal (C5a, fMLP) | Normal chemotaxis (fMLP) | 109 | ||||
| Orai1 | Heterozygous Orai+/− mice | Decreased (Tg) Decreased (fMLP) | Delayed polarization (fMLP, Tg/Ca2+); delayed arrest (fMLP, Tg/Ca2+) | 101 | |||
| Heterozygous Orai+/− mice | Decreased (fMLP, ICAM-1 in shear flow) | Reduced adhesion strengthening under flow (ICAM-1); reduced directional migration | Decreased (skin wounds) | 25, 26 | |||
| Orai1−/− bone marrow chimera | Normal (Tg) Decreased (C5a, fMLP) | Reduced chemotaxis (C5a, fMLP, LPS-primed biological fluids) | Decreased (C5a peritonitis) | 109 | |||
The table lists the neutrophil defects reported in mouse models of Stim1 and Orai1 deficiency. LysM-Cre, knock-in allele with Cre recombinase inserted into the lysozyme 2 gene; Tg, thapsigargin; IC, immune complexes; MIP-2, macrophage inflammatory protein-2; ICAM-1, intercellular adhesion molecule-1; RBC, red blood cells; Thy, thioglycollate; IMQ; imiquimod; fMLP, N-formyl-methionyl-leucyl-phenylalanine.