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-alpha), 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-alpha, or with sequential GRO-alpha/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 vs 218 +/- 33 nmol/L, P = .03). Blockade of GRO-alpha or IL-8 reversed ARDS plasma effects. After GRO-alpha/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+ influex to GRO-alpha.


CONCLUSIONS
In traumatic ARDS, plasma CXCs prime PMNs for higher [Ca2+]i flux, making PMN activation more likely. IL-8 and GRO-alpha interact to modulate these PMN [Ca2+]i responses.
Hauser
C J
CJ
Department of Surgery, UMD-New Jersey Medical School, Newark 07103, USA.
Fekete
Z
Z
Livingston
D H
DH
Goodman
E R
ER
Deitch
E A
EA
D000328:Adult; D020013:Calcium Signaling / Q000187:drug effects*; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000494:pharmacology*; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000097:blood*; D014947:Wounds and Injuries / Q000097:blood*
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8