Table 2.
Neutrophil defects in human cell lines and in STIM1 and ORAI1 deficient patients
| Gene | Manipulation | Ca2+ Signaling | Adhesion/Migration | ROS Production | Ref. No. |
|---|---|---|---|---|---|
| HL-60 cells | |||||
| STIM1 | siSTIM1 | Decreased (Tg, fMLP) | Decreased (Amplex Red, fMLP) | 14 | |
| Decreased (FcγR) | Decreased (DCFH2-yeast) | 113 | |||
| Decreased (Tg, fMLP) | Decreased polarization (fMLP) | 131 | |||
| Reduced chemotaxis (fMLP) | 112 | ||||
| STIM2 | siSTIM2 | Normal | Normal | 14 | |
| ORAI1 | siORAI1 | Decreased (Tg, fMLP) | Delayed arrest and polarization (fMLP, Tg/Ca2+) | 101 | |
| Decreased (FcγR) | Decreased (DCFH2-yeast) | 113 | |||
| Decreased adhesion strengthening to ICAM-1/E-selectin under flow | 25 | ||||
| Abrogated chemotaxis (fMLP) | 112 | ||||
| ORAI2 | siORAI2 | Normal | |||
| ORAI3 | siORAI3 | Normal | |||
| STIM1 | YFP-STIM1 overexpression | Increased (fMLP) | Increased chemotaxis (fMLP) | 112 |
| Gene | Mutation | Ca2+ Signaling | Adhesion/Migration | Phagocytosis/ROS | Cytokine Secretion | |
|---|---|---|---|---|---|---|
| Human neutrophils | ||||||
| STIM1 | p.R429C | Normal (fMLP, streptococci) | Normal (fMLP, PAF, C5a) | Normal (streptococci, zymosan) | Normal (IL-8) | (30) |
| ORAI1 | p.R91W | Normal (Tg, fMLP, streptococci) | Normal (fMLP, PAF, C5a) | Normal (streptococci, zymosan) | Normal (IL-8) | (30) |
The table lists the in vitro defects reported in neutrophil-like HL-60 cells following silencing and overexpression of STIM and ORAI isoforms, and in patients lacking functional STIM1 and ORAI1. DCFH2, 2′,7′- dichlorodihydrofluorescein; FcγR, immunoglobulin-γFc region receptor.