Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration

Zhi Ming Ding, Julia E. Babensee, Scott I. Simon, Huifang Lu, Jerry L. Perrard, Daniel C. Bullard, Xiao Y. Dai, Shannon K. Bromley, Michael L. Dustin, Mark L. Entman, C. Wayne Smith, Christie M. Ballantyne

Research output: Contribution to journalArticle

322 Scopus citations

Abstract

To differentiate the unique and overlapping functions of LFA-1 and Mac- 1, LFA-1-deficient mice were developed by targeted homologous recombination in embryonic stem cells, and neutrophil function was compared in vitro and in vivo with Mac-1-deficient, CD18-deficient, and wild-type mice. LFA-1- deficient mice exhibit leukocytosis but do not develop spontaneous infections, in contrast to CD18-deficient mice. After zymosan-activated serum stimulation, LFA-1-deficient neutrophils demonstrated activation, evidenced by up-regulation of surface Mac-1, but did not show increased adhesion to purified ICAM-1 or endothelial cells, similar to CD18-deficient neutrophils. Adhesion of Mac-1-deficient neutrophils significantly increased with stimulation, although adhesion was lower than for wild-type neutrophils. Evaluation of the strength of adhesion through LFA-1, Mac-1, and CD18 indicated a marked reduction in firm attachment, with increasing shear stress in LFA-1-deficient neutrophils, similar to CD18-deficient neutrophils, and only a modest reduction in Mac-1-deficient neutrophils. Leukocyte influx in a subcutaneous air pouch in response to TNF-α was reduced by 67% and 59% in LFA-1- and CD18-deficient mice but increased by 198% in Mac-1-deficient mice. Genetic deficiencies demonstrate that both LFA-1 and Mac-1 contribute to adhesion of neutrophils to endothelial cells and ICAM-1, but adhesion through LFA-1 overshadows the contribution from Mac-1. Neutrophil extravasation in response to TNF-α in LFA-1-deficient mice dramatically decreased, whereas neutrophil extravasation in Mac-1-deficient mice markedly increased.

Original languageEnglish (US)
Pages (from-to)5029-5038
Number of pages10
JournalJournal of Immunology
Volume163
Issue number9
StatePublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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    Ding, Z. M., Babensee, J. E., Simon, S. I., Lu, H., Perrard, J. L., Bullard, D. C., Dai, X. Y., Bromley, S. K., Dustin, M. L., Entman, M. L., Smith, C. W., & Ballantyne, C. M. (1999). Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration. Journal of Immunology, 163(9), 5029-5038.