Intracellular calcium affects neutrophil chemoattractant expression by macrophages in rats with cerulein-induced pancreatitis.
Pancreatitis complicated with infection often results in the development of multiple organ failure. We investigated the role of altered intracellular calcium as a priming signal for cytokine-induced neutrophil chemoattractant expression in this process. Agents modulating cytosolic Ca2+ were utilized to study the in vivo and in vitro cytokine-induced neutrophil chemoattractant expression for macrophages in rats with cerulein-induced pancreatitis after intraperitoneal administration of lipopolysaccharide as a septic challenge. Pretreatment with the calcium channel blocker verapamil significantly reduced serum cytokine-induced neutrophil chemoattractant concentrations in rats with cerulein-induced pancreatitis after septic challenge. Lipopolysaccharide-stimulated in vitro cytokine-induced neutrophil chemoattractant (CINC) production by peritoneal macrophages was significantly enhanced by pretreatment with thapsigargin (an inhibitor of the endoplasmic reticulum-resident Ca2+-ATPase), but not by A23187 (a calcium-specific ionophore, extracellular Ca2+ influx). Pretreatment with U73122 (a phospholipase C inhibitor) inhibited lipopolysaccharide-stimulated but not basal cytokine-induced neutrophil chemoattractant production, while verapamil (a calcium channel blocker), TMB-8 (an inhibitor of calcium release from endoplasmic reticulum), and W7 (calmodulin antagonist) completely abrogated the chemoattractant production. Altered intracellular calcium, due to Ca2+ efflux from intracellular stores, may be involved in the "priming" of macrophages to release cytokine-induced neutrophil chemoattractant following triggering with lipopolysaccharide during acute cerulein pancreatitis.
Yamaguchi
Y
Y
Department of Surgery II, Kumamoto University Medical School, Japan.
Akizuki
E
E
Matsumura
F
F
Okabe
K
K
Liang
J
J
Matsuda
T
T
Yamada
S
S
Ogawa
M
M
D000208:Acute Disease; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002108:Ceruletide; D019743:Chemokines, CXC / Q000096:biosynthesis*; D002630:Chemotactic Factors / Q000096:biosynthesis*; D006133:Growth Substances / Q000096:biosynthesis*; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D002108:Ceruletide; D002118:Calcium