Colchicine alters the quantitative and qualitative display of selectins on endothelial cells and neutrophils.

Abstract

Since colchicine-sensitive microtubules regulate the expression and topography of surface glycoproteins on a variety of cells, we sought evidence that colchicine interferes with neutrophil-endothelial interactions by altering the number and/or distribution of selectins on endothelial cells and neutrophils. Extremely low, prophylactic, concentrations of colchicine (IC5. = 3 nM) eliminated the E-selectin-mediated increment in endothelial adhesiveness for neutrophils in response to IL-1 (P < 0.001) or TNFa (P < 0.001) by changing the distribution, but not the number, of E-selectin molecules on the surface of the endothelial cells. Colchicine inhibited stimulated endothelial adhesiveness via its effects on microtubules since vinblastine, an agent which perturbs microtubule function by other mechanisms, diminished adhesiveness whereas the photoinactivated colchicine derivative y-lumicolchicine was inactive. Colchicine had no effect on cell viability. At higher, therapeutic, concentrations colchicine (IC5. = 300 nM, P < 0.001) also diminished the expression of L-selectin on the surface of neutrophils (but not lymphocytes) without affecting expression of the f2-integrin CD11b/CD18. In confirmation, L-selectin expression was strikingly reduced (relative to CD11b/CD18 expression) on neutrophils from two individuals who had ingested therapeutic doses of colchicine. These results suggest that colchicine may exert its prophylactic effects on cytokine-provoked inflammation by diminishing the qualitative expression of E-selectin on endothelium, and its therapeutic effects by diminishing the quantitative expression of L-selectin on neutrophils. (J. Clin. Invest. 1995. 96:994-1002.) Key words:

The carotid-femoral (aortic) pulse wave velocity as a marker of arterial stiffness in familial Mediterranean fever

“…It is an alkaloid that exerts its main effect at the cellular level through its interaction with tubulin at the microtubules, inhibiting the motility and exocytosis of cellular granules. Colchicine has a powerful antimitotic effect and may also decrease the expression of adhesion molecules on the surface of neutrophils and endothelial cells (33,34). Therefore, the anti-inflammatory effect of colchicine is probably due to its inhibitory effect on leukocyte chemotaxis (35).…”

Salicylates Inhibit T Cell Adhesion on Endothelium Under Nonstatic Conditions: Induction of L-Selectin Shedding by a Tyrosine Kinase-Dependent Mechanism

“…L-selectin shedding not only occurs in response to cell activation, but also after treatment with nonactivating agents such as mAb against signal-transducing molecules promoting cell aggregation (53, 54) chemical cross-linkers (55), acute phase reactants (56), or drugs with anti-inflammatory properties, including colchicine (57)(58)(59). Although the signaling mechanisms regulating Lselectin shedding are largely undefined, it has been shown that the cleavage of this molecule from the T cell surface can be triggered through multiple independent intracellular signaling pathways that may depend on either PKC or PTK activity (25,45,53,60).…”

Evaluation of Anti Arthritic Potential of Gloriosa superba (L.) Elite Germplasm Collected from Eastern Himalayas, India

“…Specifically, it is attributed due to various proposed actions as disruption of microtubule in neutrophils and inhibiting their migration towards the chemotactic factors, alteration in distribution of adhesion molecules on the surface of both neutrophils and endothelial cells, which significantly inhibit the interaction between WBC and endothelial cells, inhibition of monosodium urate crystal activation of the NLRP3 inflammasome, inhibit the release of IL-1β and suppression of gene expression. 12,13,14,15 This however is dependent upon the dose of colchicine and duration of treatment; the effect is at both molecular and genetic level. 25 The competitive binding of colchicine to serum albumin was well established 26 and thus supports the selection of appropriate method in study to check the existing variability in targeted pharmaco logical activity.…”