LFA-1 is sufficient in mediating neutrophil emigration in Mac-1-deficient mice.

Abstract

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 Ͼ 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. ( J. Clin. Invest. 1997. 99:1340-1350.)

Combinatorial requirements for adhesion molecules in mediating neutrophil emigration during bacterial peritonitis in mice

“…Antibodies against CD11a/CD18 decreased neutrophil emigration by 82% during 4 h of streptococcal peritonitis. Similar results have been observed with antibodies against CD11a/ CD18 during thioglycollate peritonitis in mice [15] or rabbits [14], and during glycogen peritonitis in rabbits [13]. Mutant mice deficient in CD11a have decreased neutrophil emigration after 4 h of thioglycollate peritonitis [16].…”

“…CD11a/CD18 is critical to neutrophil emigration during peritonitis, as demonstrated by blocking antibody studies [13][14][15] and by CD11a deficiency [16]. CD11b/CD18 also binds ICAM-1 [17,18].…”

“…CD11b/CD18 also binds ICAM-1 [17,18]. The role of CD11b/CD18 in neutrophil emigration during peritonitis is not yet clear [15,[19][20][21][22].…”

The immune system and cardiac repair

“…Antibodies that inhibit LFA-1 adhesion are effective in blocking transmigration [193] and LFA-1 deficient mice show dramatically decreased neutrophil extravasation at sites of inflammation [194]. In contrast, antibodies that block Mac-1 adhesion are marginally effective [193], and Mac-1 deficient mice demonstrate no deficit in neutrophil emigration [195]. These findings suggest that LFA-1 and not Mac-1 is critical for neutrophil extravasation in sites of inflammation.…”

Stimulus-Dependent Impairment of the Neutrophil Oxidative Burst Response in Lactoferrin-Deficient Mice

“…Analysis of neutrophil migration to the peritoneal cavity after thioglycollate administration was performed as described by Lu and colleagues 51 with minor modifications. Briefly, WT and LFKO mice were injected intraperitoneally with 3% thioglycollate media (1 ml) and were euthanized at 0 or 4 hours after injection.…”