The roles of selectins in the pulmonary margination and emigration of neutrophils were investigated by using mice genetically deficient in both E- and P-selectins (E/P mutants) and/or by intravenous injections of fucoidin (inhibiting both L- and P-selectins). E/P mutants were neutrophilic (14.7 +/- 4.9 x 10(6) vs. 0.8 +/- 0.1 x 10(6) neutrophils/ml). This neutrophilia was associated with increa...

Cell adhesion to endothelium regulates the trafficking and recruitment of leukocytes towards lymphoid organs and sites of inflammation. This phenomenon is mediated by the expression of a number of adhesion molecules on both the endothelium and circulating cells. Activation of endothelial cells (EC) with different stimuli induces the expression of several adhesion molecules (E- and P-selectins, ...

Background & objective Pruritus is the most frequent chronic dermal complication of sulfur mustard (SM), which negatively influences the quality of life. Exact pathophysiology of SM-induced itching is unknown. The current study aimed at evaluating the possible association between SM-induced itching and the serum levels of matrix metalloproteinase (MMP)-9 and their endogenous inhibitors, and ser...

INTRODUCTION One of the main histopathological features of alopecia areata (AA) is a lymphocytic infiltration that surrounds hair follicles. Soluble forms of E, L, P-selectins are known indicators of ongoing inflammation. There are no studies regarding the assessment of their contribution in AA. AIM To assess serum concentrations of selectins (E-selectin, L-selectin and P-selectin) in patient...

ACCOMPLISHMENTS (throughout the award period): We first established the model system for analyzing IgEand mast cell-dependent cutaneous allergic reactions in wild type (normal) mice of the correct genetic background (129/Sv x C57BL/6 mice), since the details of the methods needed for optimal analysis of such reactions can vary according to mouse strain. We then analyzed multiple features of IgE...

A multistep series of adhesive and signaling events regulates inflammatory responses to infection or injury (1–3). To initiate these responses, circulating leukocytes must adhere to the vascular wall under shear forces. Selectins mediate the first adhesive step, which is characterized by tethering and rolling of leukocytes on endothelial cells, platelets, or other leukocytes (4, 5). L-selectin,...

Two mechanisms have been proposed for regulating rolling velocities on selectins. These are (a) the intrinsic kinetics of bond dissociation, and (b) the reactive compliance, i.e., the susceptibility of the bond dissociation reaction to applied force. To determine which of these mechanisms explains the 7.5-11.5-fold faster rolling of leukocytes on L-selectin than on E- and P-selectins, we have c...

Leukocyte accumulation in cerebrospinal fluid and disruption of the blood-brain barrier are central components of meningitis and are associated with a poor prognosis. Genetically engineered deficiencies or functional inhibition of endothelial leukocyte adhesion receptors P-, or P- plus E-selectins, lead to deficits in leukocyte rolling and extravasation. However, their impact on meningeal infla...

Selectins mediate tethering and rolling of leukocytes to the vascular endothelium, the first adhesive step in the recruitment of immune cells to inflamed tissues. Thus, selectins play a key role in the pathogenesis of common inflammatory skin disorders such as atopic dermatitis or psoriasis. As a consequence of their key functions, selectins have received much attention as potential target stru...

We previously showed that intercellular adhesion molecule-1 (ICAM-1) expression by the host is essential for lymphoma dissemination. Because selectins usually act in a coordinated fashion with ICAM-1 in the recruitment of circulating normal cells, we investigated their implication in lymphomagenesis and metastasis. Using selectin-deficient mice, we found that though the absence of E-, P-, or L-...