Myeloid cell function in MRP-14 (S100A9) null mice.
Myeloid-related protein 14 (MRP-14) and its heterodimeric partner, MRP-8, are cytosolic calcium-binding proteins, highly expressed in neutrophils and monocytes. To understand the function of MRP-14, we performed targeted disruption of the MRP-14 gene in mice. MRP-14(-/-) mice showed no obvious phenotype and were fertile. MRP-8 mRNA but not protein is present in the myeloid cells of these mice, suggesting that the stability of MRP-8 protein is dependent on MRP-14 expression. A compensatory increase in other proteins was not detected in cells lacking MRP-8 and MRP-14. Although the morphology of MRP-14(-/-) myeloid cells was not altered, they were significantly less dense. When Ca(2+) responses were investigated, there was no change in the maximal response to the chemokine MIP-2. At lower concentrations, however, there was reduced responsiveness in MRP-14(-/-) compared with MRP-14(+/+) neutrophils. This alteration in the ability to flux Ca(2+) did not impair the ability of the MRP-14(-/-) neutrophils to respond chemotactically to MIP-2. In addition, the myeloid cell functions of phagocytosis, superoxide burst, and apoptosis were unaffected in MRP-14(-/-) cells. In an in vivo model of peritonitis, MRP-14(-/-) mice showed no difference from wild-type mice in induced inflammatory response. The data indicate that MRP-14 and MRP-8 are dispensable for many myeloid cell functions.
Hobbs
Josie A R
JA
Leukocyte Adhesion Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, London WC2A 3PX, United Kingdom.
May
Richard
R
Tanousis
Kiki
K
McNeill
Eileen
E
Mathies
Margaret
M
Gebhardt
Christoffer
C
Henderson
Robert
R
Robinson
Matthew J
MJ
Hogg
Nancy
N
D000818:Animals; D002118:Calcium / Q000378:metabolism; D040501:Calgranulin A / Q000096:biosynthesis / Q000235:genetics; D040502:Calgranulin B / Q000235:genetics / Q000502:physiology*; D002452:Cell Count; D002478:Cells, Cultured; D054426:Chemokine CXCL2; D018925:Chemokines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010538:Peritonitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis
D040501:Calgranulin A; D040502:Calgranulin B; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D005456:Fluorescent Dyes; D012333:RNA, Messenger; D002118:Calcium