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

Huifang Lu, C. Wayne Smith, Jerry Perrard, Dan Bullard, Li Ping Tang, Scott B. Shappell, Mark L. Entman, Arthur L. Beaudet, Christie M. Ballantyne

Research output: Contribution to journalArticle

247 Citations (Scopus)

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 > 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.

Original languageEnglish (US)
Pages (from-to)1340-1350
Number of pages11
JournalJournal of Clinical Investigation
Volume99
Issue number6
DOIs
StatePublished - Mar 15 1997

Fingerprint

Lymphocyte Function-Associated Antigen-1
Emigration and Immigration
Neutrophils
Fibrinogen
Peritoneal Cavity
Complement C3b
Thioglycolates
Mutation
Homologous Recombination
Ribonucleases
Southern Blotting
Phagocytosis
Integrins
Glass
Flow Cytometry
Immunohistochemistry

Keywords

  • cell adhesion molecules
  • cell degranulation
  • fibrinogen
  • inflammation
  • integrins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lu, H., Smith, C. W., Perrard, J., Bullard, D., Tang, L. P., Shappell, S. B., ... Ballantyne, C. M. (1997). LFA-1 is sufficient in mediating neutrophil emigration in Mac-1- deficient mice. Journal of Clinical Investigation, 99(6), 1340-1350. https://doi.org/10.1172/JCI119293

LFA-1 is sufficient in mediating neutrophil emigration in Mac-1- deficient mice. / Lu, Huifang; Smith, C. Wayne; Perrard, Jerry; Bullard, Dan; Tang, Li Ping; Shappell, Scott B.; Entman, Mark L.; Beaudet, Arthur L.; Ballantyne, Christie M.

In: Journal of Clinical Investigation, Vol. 99, No. 6, 15.03.1997, p. 1340-1350.

Research output: Contribution to journalArticle

Lu, H, Smith, CW, Perrard, J, Bullard, D, Tang, LP, Shappell, SB, Entman, ML, Beaudet, AL & Ballantyne, CM 1997, 'LFA-1 is sufficient in mediating neutrophil emigration in Mac-1- deficient mice', Journal of Clinical Investigation, vol. 99, no. 6, pp. 1340-1350. https://doi.org/10.1172/JCI119293
Lu, Huifang ; Smith, C. Wayne ; Perrard, Jerry ; Bullard, Dan ; Tang, Li Ping ; Shappell, Scott B. ; Entman, Mark L. ; Beaudet, Arthur L. ; Ballantyne, Christie M. / LFA-1 is sufficient in mediating neutrophil emigration in Mac-1- deficient mice. In: Journal of Clinical Investigation. 1997 ; Vol. 99, No. 6. pp. 1340-1350.
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