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Content Provider | IEEE Xplore Digital Library |
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Author | Forlow, S.B. Ley, K. |
Copyright Year | 1999 |
Description | Author affiliation: Dept. of Biomed. Eng., Virginia Univ., Charlottesville, VA, USA (Forlow, S.B.) |
Abstract | L-, E-, and P-selectin mediate the majority of leukocyte capture and rolling on the inflamed vessel wall. We have recently shown that leukocyte rolling and adherence is drastically reduced in mice lacking L-, E-, and P-selectin (L/E/P-/-) and in mice lacking E- and P-selectin and ICAM-1 (E/P/I-/-). Here, we have generated mice deficient in four adhesion molecules (L-, E- and P-selectin and ICAM-1) to further investigate selectin-independent mechanisms of leukocyte rolling and adhesion in a TNF-/spl alpha/ (0.5 /spl mu/g, 6 hr) induced model of inflammation of the cremaster muscle. The quadruple knockouts (L/E/P/I-/-) were made by transplanting L-/- bone marrow into lethally irradiated E/P/I-/-. Leukocyte rolling flux was 2 min/sup -1/ in L/E/P/I-/-compared to 77 min/sup -1/ in wild-type mice. Residual leukocyte rolling was completely removed after the administration of an /spl alpha//sub 4/ integrin blocking antibody. Injecting /spl alpha//sub 4/ blocking antibody at the time of TNF-/spl alpha/ also reduced leukocyte adhesion (59 mm/sup -2/) compared to L/E/P/I-/- (396 mm/sup -2/) and wild-type (1,080 mm/sup -2/) mice. The only significant accumulation in L/E/P/I-/- occurred at confluent branch points where the fluid flow regime is likely altered. This leukocyte adhesion is selectin-independent and also occurred in mice pretreated with an /spl alpha//sub 4/ integrin blocking antibody. These data show some leukocyte adherence can occur without rolling through selectin and /spl alpha//sub 4/ integrin-independent mechanisms. This recruitment mechanism is confined to venular branch points. |
File Size | 135504 |
File Format | |
ISBN | 0780356748 |
ISSN | 1094687X |
DOI | 10.1109/IEMBS.1999.802081 |
Language | English |
Publisher | Institute of Electrical and Electronics Engineers, Inc. (IEEE) |
Publisher Date | 1999-10-13 |
Publisher Place | USA |
Access Restriction | Subscribed |
Rights Holder | Institute of Electrical and Electronics Engineers, Inc. (IEEE) |
Subject Keyword | White blood cells Adhesives Mice Bones Muscles Fluid flow Biomedical engineering Recruitment Veins Anesthetic drugs |
Content Type | Text |
Resource Type | Article |
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