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PMID:10528208
| Citation |
Ding, ZM, Babensee, JE, Simon, SI, Lu, H, Perrard, JL, Bullard, DC, Dai, XY, Bromley, SK, Dustin, ML, Entman, ML, Smith, CW and Ballantyne, CM (1999) Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration. J. Immunol. 163:5029-38 |
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| 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-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. |
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| Keywords |
Animals; Antigens, CD18/biosynthesis; Cell Adhesion/immunology; Cell Movement/immunology; Chemotaxis, Leukocyte; Diffusion Chambers, Culture; Female; Injections, Subcutaneous; Interphase/immunology; Lymphocyte Activation/immunology; Lymphocyte Function-Associated Antigen-1/biosynthesis; Lymphocyte Function-Associated Antigen-1/genetics; Lymphocyte Function-Associated Antigen-1/physiology; Macrophage-1 Antigen/biosynthesis; Macrophage-1 Antigen/physiology; Male; Membrane Proteins/biosynthesis; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils/immunology; Neutrophils/metabolism; Neutrophils/physiology; Stress, Mechanical; Tumor Necrosis Factor-alpha/pharmacology |
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Significance
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