LFA-1 is sufficient in mediating neutrophil emigration in Mac-1-deficient mice.
To better define the specific function of Mac-1 (CD11b) versus LFA-1 (CD11a) and the other CD11 integrins in vivo, we have disrupted murine CD11b by targeted homologous recombination in embryonic stem cells and generated mice which are homozygous for a mutation in CD11b. A null mutation was confirmed by Southern blotting, RNase protection assay, immunohistochemistry, and flow cytometry. Neutrophils isolated from mice deficient in Mac-1 were defective in adherence to keyhole limpet hemocyanin-coated glass, iC3b-mediated phagocytosis, and homotypic aggregation. When challenged by thioglycollate intraperitoneally, Mac-1-deficient mice had similar levels of neutrophil accumulation in the peritoneal cavity at 1, 2, and 4 h. Treatment with mAb to LFA-1 blocked 78% of neutrophil accumulation in Mac-1-deficient mice and 58% in wild-type mice. Neutrophil emigration into the peritoneal cavity 16 h after the implantation of fibrinogen-coated disks was not reduced in Mac-1-deficient mice whereas neutrophil adhesion to the fibrinogen-coated disks was reduced by > 90%. Neutrophils from Mac-1-deficient mice also showed reduced degranulation. Our results demonstrate that Mac-1 plays a critical role in mediating binding of neutrophils to fibrinogen and neutrophil degranulation, but is not necessary for effective neutrophil emigration, which is more dependent upon LFA-1.
Lu
H
H
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
Smith
C W
CW
Perrard
J
J
Bullard
D
D
Tang
L
L
Shappell
S B
SB
Entman
M L
ML
Beaudet
A L
AL
Ballantyne
C M
CM
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D015550:Cell Degranulation; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D007700:Kinetics; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D010538:Peritonitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells; D013864:Thioglycolates
D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D013864:Thioglycolates