Granulocyte function in grancalcin-deficient mice.
Grancalcin, one of the penta-EF-hand Ca(2+) binding proteins, is expressed at high levels in polymorphonuclear granulocytes (neutrophils). EF-hand proteins are implicated in the regulation of diverse processes including cell migration, apoptosis, and mobilization of neutrophil effector functions. To determine the role of grancalcin in vivo, we inactivated the gene encoding grancalcin (Gca) in embryonic stem cells and generated grancalcin-deficient mice. Homozygous Gca mutants appeared healthy and reproduced normally. Leukocyte recruitment into the peritoneal cavity upon induction of inflammation was not significantly affected by the absence of grancalcin. The mutants also resisted systemic fungal infection similarly to wild-type mice, and in vitro killing of Staphylococcus aureus by inflammatory cells was not significantly impaired. While marginally increased survival rates of mutants faced with endotoxic shock may indicate a contribution of grancalcin to immunopathogenesis, it is not essential for vital leukocyte effector functions required to control microbial infections.
Roes
Jürgen
J
Department of Immunology and Molecular Pathology, Windeyer Institute of Medical Sciences, University College London, London W1T 4JF, United Kingdom. j.roes@ucl.ac.uk
Choi
B Ken
BK
Power
David
D
Xu
Ping
P
Segal
Anthony W
AW
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D002177:Candidiasis / Q000503:physiopathology; D015550:Cell Degranulation; D018076:DNA, Complementary / Q000235:genetics; D018390:Gene Targeting; D006098:Granulocytes / Q000473:pathology / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000473:pathology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000473:pathology / Q000502:physiology; D010538:Peritonitis / Q000473:pathology / Q000503:physiopathology; D012772:Shock, Septic / Q000503:physiopathology; D013203:Staphylococcal Infections / Q000503:physiopathology
D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; C503122:Gca protein, mouse