Leukocyte rolling is exclusively mediated by P-selectinin colonic venules.

• 1. The objective of the present study was to examine the role of the endothelial selectins (i.e. P- and E-selectin) in leukocyte-endothelium interactions in colonic venules by use of intravital microscopy. 2. Balb/c mice were exposed to dextran sodium sulphate (DSS) in the drinking water for 5 days or treated intraperitoneally (i.p.) with tumour necrosis factor-alpha (TNF-alpha) for 3 h. 3. In DSS-treated mice, mRNA of both P- and E-selectin were expressed and leukocyte rolling and adhesion was increased to 27+/-3 cells min(-1) and 36+/-8 cells mm(-1), respectively. An anti-P-selectin antibody abolished DSS-induced leukocyte rolling, whereas an antibody against E-selectin had no effect. Established leukocyte adhesion was insensitive to inhibition of the selectins. 4. DSS markedly increased production of TNF-alpha in the colon. TNF-alpha increased leukocyte rolling to 22+/-3 cells min(-1) and adhesion to 45+/-4 cells mm(-1). Only inhibition of P-selectin significantly reduced (>94%) leukocyte rolling provoked by TNF-alpha. Leukocyte adhesion was not changed by late anti-P-selectin antibody treatment. In contrast, pretreatment with the anti-P-selectin antibody not only abolished leukocyte rolling but also completely inhibited firm adhesion in response to TNF-alpha. 5. This study demonstrates that P-selectin plays an important role in leukocyte rolling in colonic venules, both in experimental colitis and when stimulated with TNF-alpha. Moreover, P-selectin-dependent leukocyte rolling was found to be a precondition for TNF-alpha-induced firm adhesion. Thus, these findings suggest that P-selectin may be a key target to reduce pathological recruitment of inflammatory cells in the colon.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Keyword

Dextran Sulfate : pharmacology

Animal

Disease Models

E-Selectin : genetics

E-Selectin : metabolism

E-Selectin : physiology

Leukocytes : drug effects

Leukocytes : physiology

Male

Mice

Inbred BALB C

P-Selectin : genetics

P-Selectin : metabolism

RNA

P-Selectin : physiology

Messenger : metabolism

Support

Non-U.S. Gov't

Tumor Necrosis Factor : pharmacology

Venules : cytology

Venules : physiology

Colitis : pathology

Colitis : chemically induced

Cell Adhesion : physiology

Publication and Content Type

art (subject category)

ref (subject category)