Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration
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-defici...
| Autori principali: | , , , , , , , , , , , |
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| Natura: | Journal article |
| Lingua: | English |
| Pubblicazione: |
American Association of Immunologists, Inc.
1999
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| _version_ | 1826301577673048064 |
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| author | Ding, Z Babensee, J Simon, S Lu, H Perrard, J Bullard, D Dai, X Bromley, S Dustin, M Entman, M Smith, C Ballantyne, C |
| author_facet | Ding, Z Babensee, J Simon, S Lu, H Perrard, J Bullard, D Dai, X Bromley, S Dustin, M Entman, M Smith, C Ballantyne, C |
| author_sort | Ding, Z |
| collection | OXFORD |
| description | 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-alpha 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-alpha in LFA-1-deficient mice dramatically decreased, whereas neutrophil extravasation in Mac-1-deficient mice markedly increased. |
| first_indexed | 2024-03-07T05:34:31Z |
| format | Journal article |
| id | oxford-uuid:e36c8fd3-6dd6-4a70-a9f1-1d30f00c1c90 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:34:31Z |
| publishDate | 1999 |
| publisher | American Association of Immunologists, Inc. |
| record_format | dspace |
| spelling | oxford-uuid:e36c8fd3-6dd6-4a70-a9f1-1d30f00c1c902022-03-27T10:09:02ZRelative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migrationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e36c8fd3-6dd6-4a70-a9f1-1d30f00c1c90EnglishSymplectic Elements at OxfordAmerican Association of Immunologists, Inc.1999Ding, ZBabensee, JSimon, SLu, HPerrard, JBullard, DDai, XBromley, SDustin, MEntman, MSmith, CBallantyne, CTo 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-alpha 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-alpha in LFA-1-deficient mice dramatically decreased, whereas neutrophil extravasation in Mac-1-deficient mice markedly increased. |
| spellingShingle | Ding, Z Babensee, J Simon, S Lu, H Perrard, J Bullard, D Dai, X Bromley, S Dustin, M Entman, M Smith, C Ballantyne, C Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration |
| title | Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration |
| title_full | Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration |
| title_fullStr | Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration |
| title_full_unstemmed | Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration |
| title_short | Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration |
| title_sort | relative contribution of lfa 1 and mac 1 to neutrophil adhesion and migration |
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