Dictionary of Allergies .. Adhesion molecules

Adhesion molecules

Essential components of immunity response and inflammation. Adhesion molecules could be classified as integrins, selectins, immunoglobulins superfamily and carbohydrates. Adhesion molecules have an important role in immune response and different inflammatory diseases. Interactions between leucocytes, macrophages, endothelial cells and platelets are mediated by adhesion molecules. The role of these molecules in inflammation, graft rejection, cancer and hemostasis is now being studied. Leucocytes circulate as non-adherent cells in blood and migrate as adherent cells through tissues. These interactions are facilitated by three families of adhesion receptors:

1) the immunoglobulin superfamily which includes the antigen-specific receptors of T and B lymphocytes.

2) The intracellular cell adhesion molecule-1 (ICAM-1) which is expressed on the surface of vascular endothelial cells and the vascular - cell adhesion molecule-1 (VCAM-1). Recent studies have revealed that interleukin (IL)-13, as well as IL-4, causes de novo surface expression of vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells of the umbilical vein and accelerates selective eosinophil migration. However, its role in allergic rhinitis remains to be clarified [1].

3) The integrin family which include the lymphocyte function related antigen (LFA-1), the macrophage antigen1 (Mac-1), and p150,95 which expressed on eosinophils.

4) The selectins which are prominent in lymphocyte and neutrophil interaction with vascular endothelium[2],. The adhesion molecules have several functions but some of them are used as receptors by viruses. Proinflammatory mediators initiate a complex network of inflammatory phenomena involving adhesion molecules, Th2 T lymphocytes (which mainly release IL-4, IL-5, and IL-13), cytokines, and mediators [3] . These result in the late and ongoing allergic symptoms of nasal congestion, asthma, and urticaria. Adhesion molecules are involved in the recruitment of inflammatory cells (eosinophils, basophils, and neutrophils) from the circulation to the site of the inflammatory reaction. Specific adhesion molecules favour the tether/roll of inflammatory cells towards the epithelium (e.g. vascular cellular adhesion molecule-1 (VCAM-1), P-selectin, and L-selectin), the firm arrest of inflammatory cells to the epithelium (e.g. CD18 integrin, intercellular adhesion molecule-1 (ICAM-1), and VCAM-1), and diapedesis (migration) through the epithelium[4]. Therapeutic strategies for interventions with monoclonal antibodies and their derivatives and soluble forms of adhesion molecules could now be planned. Finally the diagnostic potential of adhesion molecules detection "in vivo" and ex vivo" is a field of growing importance for a better management of inflammatory disease[5]. Tissue eosinophilia is one of the hallmarks of allergic diseases and Th2-type immune responses including asthma. Adhesion molecules are known to play an important role in the accumulation of eosinophils in allergic inflammatory foci, and they contribute to eosinophil activation. Elevated levels of the soluble forms of adhesion molecules in the body fluid of asthmatic patients have been observed, although their pathophysiological significance remains to be fully elucidated[6]. (Þ also: Leukocyte Adhesion Molecules; Asthma, molecular mechanisms involved in asthmatic airway inflammation).

References

1. Bousquet J, Van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001;108(Suppl. 5):S147-S334.

2. Kanwar S, Johnston B, Kubes P. Leukotriene C4/D4 induces P-selectin and sialyl Lewis(x)-dependent alterations in leukocyte kinetics in vivo. Circ Res 1995;77: 879-887.

3. Palma-Carlos, A.G., Palma-Carlos, M.L.: Adhesion molecules in immunity and inflammation. Allergie et Immunologie. Vol. 25, No.1, p. 4, 1993.

4. Springer, T.A.: Adhesion receptors of the immune system, Nature 1990:346:425.

5. Terada, N. Et al: The potential role of interleukin-13 in eosinophilic inflammation in nasal mucosa. Allergy 1998:53:690-697.

6. Ueki S, Kihara J, Kato H, Ito W, Takeda M, Kobayashi Y, Kayaba H, Chihara J.Soluble vascular cell adhesion molecule-1 induces human eosinophil migration. Allergy. 2009 Feb 10.