Injury-enhanced calcium mobilization in circulating rat neutrophils models human PMN responses.
G-protein coupled (GPC) chemoattractants are important neutrophil (PMN) activators in human shock and sepsis, acting in part by increasing cytosolic calcium ([Ca2+]i). Rats are widely used as laboratory models of shock and sepsis, but reports of [Ca2+]i flux in circulating rat PMN are rare. Moreover, the [Ca2+]i values reported often differ markedly from human systems. We developed study methods where basal [Ca2+]i values in circulating rat PMN were comparable to human PMN, but rat PMN still mobilized calcium poorly after stimulation. Trauma (laparotomy) did not change rat PMN basal [Ca2+]i, but induced brisk [Ca2+]i responses to chemokine and lipid mediators that approximated human PMN responses. This was associated with marked loading of microsomal calcium stores. Formyl peptides still mobilized calcium less well in rat than human PMN. Normal rat PMN appear to circulate in a less mature or primed form than human PMN. A very limited injury rapidly converts rat PMN to a more activated phenotype. PMN thus activated act quite similar to human PMN in terms of GPC receptor-mediated calcium mobilization. Trauma enhances rat PMN responses to GPC agonists at least in part by loading cell calcium stores.
Fekete
Z
Z
Department of Surgery, UMD-New Jersey Medical School, Newark 07103, USA.
Hauser
C J
CJ
Adams
J M
JM
Adams
C A
CA
Forsythe
R M
RM
Haskó
G
G
Xu
D Z
DZ
Livingston
D H
DH
Deitch
E A
EA
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007813:Laparotomy; D008297:Male; D009504:Neutrophils / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014947:Wounds and Injuries / Q000378:metabolism*
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; C513297:Cxcl1 protein, rat; C404915:Cxcl2 protein, mouse; C513296:Cxcl2 protein, rat; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D019204:GTP-Binding Proteins; D002118:Calcium