Monocyte activation: rapid induction of α1/β1 (VLA‐1) integrin expression by lipopolysaccharide and interferon‐γ

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Abstract
Monocytes play a key role in inflammation, tissue injury and remodelling and wound healing, and most monocyte effector functions are dependent on adhesive interactions. We have analyzed the changes in the pattern of β1 integrin expression that take place during monocyte activation and demonstrated that lipopolysaccharide (LPS) and interferon (IFN)-γ specifically induce the expression of the α1/β1 integrin, which was detectable on the monocyte membrane as early as 12 h after monocyte activation. The up-regulated α1/β1 expression was not dependent on monocyte adherence to solid surfaces, and Northern blot analysis revealed that LPS and IFN-γ induce the α1 mRNA de novo. Monocyte deactivating cytokines such as interleukin (IL)-4 or IL-10, could only minimally inhibit the LPS- or IFN-γ mediated up-regulation of α1/β1, suggesting that cytokine release subsequent to monocyte activation does not play a major role in the integrin induction. Interestingly, the LPS-induced expression of α1/β1 was found to be dependent on the redox state of the cell, since it was inhibited by antioxidants which also altered the morphological changes that take place during monocyte culture in vitro. The rapid induction of α1 in LPS-activated monocytes suggests that α1/β1 might be involved not only in monocyte/extracellular matrix interactions during inflammatory reactions, but also in contributing to further monocyte activation and cytokine production during septic shock syndrome.