| First Author | Lu H | Year | 1997 |
| Journal | J Clin Invest | Volume | 99 |
| Issue | 6 | Pages | 1340-50 |
| PubMed ID | 9077544 | Mgi Jnum | J:39092 |
| Mgi Id | MGI:86473 | Doi | 10.1172/JCI119293 |
| Citation | Lu H, et al. (1997) LFA-1 is sufficient in mediating neutrophil emigration in Mac-1-deficient mice. J Clin Invest 99(6):1340-50 |
| abstractText | 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. |
