On mouse and man: neutrophil gelatinase associated lipocalin is not involved in apoptosis or acute response.
Neutrophil gelatinase-associated lipocalin (NGAL) is a siderphore binding molecule present in the specific granules of neutrophils and induced in a variety of epithelial cells during inflammation. Its mouse orthologue, 24p3, is also an acute phase protein synthesized in the liver and adipose tissue during inflammation. 24p3 has recently been implicated in apoptosis of myeloid cells. We investigated whether similar features are characteristics of NGAL. First, isolated normal myeloid bone marrow cells were incubated with NGAL for 6 and 24 hr and analyzed for apoptosis by annexin V binding and by propidium iodide labeling. We found no indication that NGAL induces significant apoptosis in myeloid cells. Second, a human sepsis model where normal volunteers were given endotoxin 2 ng/kg intravenously, showed no evidence that NGAL is an acute phase protein. The plasma level of NGAL reflected the number of circulating neutrophils and was completely different from the kinetics of C-reactive protein. We thus conclude that major differences exist between mouse and man with regards to the role of this lipocalin in myelopoiesis and inflammation.
Klausen
Pia
P
Department of Hematology, The Granulocyte Research Laboratory, Rigshospitalet 9322, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark. pia.klausen@rh.hosp.dk
Niemann
Carsten U
CU
Cowland
Jack B
JB
Krabbe
Karen
K
Borregaard
Niels
N
D000209:Acute-Phase Proteins / Q000494:pharmacology*; D000210:Acute-Phase Reaction; D000818:Animals; D017209:Apoptosis; D001772:Blood Cell Count; D001854:Bone Marrow Cells; D002097:C-Reactive Protein / Q000032:analysis; D002478:Cells, Cultured; D004731:Endotoxins / Q000008:administration & dosage; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins; D051379:Mice; D022423:Myeloid Cells / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology; D015513:Oncogene Proteins / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000494:pharmacology*; D018805:Sepsis / Q000097:blood / Q000139:chemically induced; D013045:Species Specificity
D000209:Acute-Phase Proteins; D004731:Endotoxins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; C071332:Lcn2 protein, mouse; D002097:C-Reactive Protein