Integrated stimulation by CXC chemokines enhances PMN [Ca²⁺](i) signaling in trauma and adult respiratory distress syndrome

Background. Trauma and adult respiratory distress syndrome (ARDS) are associated with increased CXC chemokine (CXC) activity. CXCs such as interleukin (IL)-8 activate polymorphonuclear neutrophils (PMNs) in the lung by means of calcium signals ([Ca²⁺](i)). We studied CXC effects on PMN [Ca²⁺](i) in ARDS and trauma. Methods. Isolated PMNs were loaded with Fura- 2 dye. Normal PMNs were incubated in ARDS plasma or volunteer plasma, with or without blocking antibodies to IL-8, growth-related oncogene alpha (GRO-α), or both (n = 6 pairs), and then stimulated with 1 to 10 nmol/L IL-8. PMNs from trauma patients or volunteers (n = 10 pairs) were stimulated with GRO- α, or with sequential GRO-α/IL-8. [Ca²⁺](i) was measured with spectrofluorometry. Results. [Ca²⁺](i) responses to IL-8 were higher after being incubated in ARDS plasma than in volunteer plasma (251 ± 33 v s 218 ± 33 nmol/L, P = .03). Blockade of GRO-α IL-8 reversed ARDS plasma effects. After GRO-α/IL-8, PMNs from trauma patients demonstrated more Ca²⁺ store release than did PMNs from volunteers (235 ± 13 vs 170 ± 10 nmol/L, P < .01). Conversely, PMNs from trauma patients lost receptor-operated Ca²⁺ influx to GRO-α. Conclusions. In traumatic ARDS, plasma CXCs prime PMNs for higher [Ca²⁺](i) flux, making PMN activation more likely. IL-8 and GRO-α interact to modulate these PMN [Ca²⁺](i) responses.