β2 Integrin/ICAM-1 adhesion molecule interactions in cutaneous inflammation and tumor promotion.

Autor: Oberyszyn, TM, Conti, CJ, Ross, MS, Oberyszyn, AS, Tober, KL, Rackoff, AI, Robertson, FM
Zdroj: Carcinogenesis; Mar1998, Vol. 19 Issue 3, p445-455, 11p
Abstrakt: The β2 integrin (CD 18/CD 11 a, b, c) family of proteins mediate adherence of leukocytes to vascular endothelium and the associated ligand, intercellular adhesion molecules-1 (ICAM-1; CD 54), interacts with β2 integrin proteins to allow transendothelial migration of leukocytes into sites of inflammation. The present study examines the function of these proteins in a murine model of acute cutaneous inflammation induced following topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) to the dorsal epidermis of SENCAR mice and in a model of skin multistage carcinogenesis. At 24 h following topical application of TPA to the dorsal epidermis of mice, dermal leukocytes expressed higher levels of β2 integrin protein compared with the lower levels of β2 integrin protein expression by peripheral blood leukocytes. ICAM-1 protein was localized to epidermal keratinocytes and vascular endothelium in TPA-treated skin and to proliferating papilloma cells. Intravenous (i.v.) injection of either 50 μg anti-β2 integrin antibody alone or in combination with anti-ICAM-1 antibody significantly inhibited both TPA-stimulated neutrophil infiltration into the dermis (P <0.001) and myeloperoxidase (MPO) activity (P <0.03 anti-β2 integrin antibody; P <0.01 anti-β2 integrin + ICAM-1 adhesion molecule antibodies), but had no effect on TPA-induced epidermal hyperplasia. In addition, injection of either anti-ICAM-1 adhesion molecule antibody alone (P <0.004) or in combination with anti-β2 integrin antibody (P <0.001) significantly inhibited TPA-induced production of 7,8-dihydroxy-2'-deoxyguanosine (8-OHdG) immunoreactive proteins by epidermal keratinocytes. β2 Integrin/ICAM-1 adhesion molecules work in concert to regulate migration, retention and functional activation of leukocytes within the dermis during TPA-induced skin inflammation and within stromal tissue of papillomas that form during multi-stage carcinogenesis. Agents that inhibit these receptor/ligand interactions may be useful in defining the roles of specific state carcinogenesis and may also have potential as anti-promoting and anti-progression agents. [ABSTRACT FROM PUBLISHER]
Databáze: Complementary Index