Integrin Crosstalk Regulation of Human Neutrophils Adhered to Fibronectin and Beta‐glucan

Abstract

Complement Receptor 3 (CR3), an integrin found on neutrophils, plays an important role in fungal recognition. Co‐ligation of CR3 with fibronectin (Fn) at the I‐domain and β‐glucan (B) at the lectin‐like domain is possible due to spatially distinct locations. Dual ligation of CR3 with Fn+B induces homotypic aggregation of primed neutrophils, a response representative of the immune cells encounter with fungi within tissues. To understand the molecular mechanisms involved in this response, we explored the role of other integrins and intercellular signaling molecules. Antibody blockade of VLA3, the canonical laminin receptor, showed abrogation of aggregate formation on immobilized Fn+B. VLA3 did not show an effect on either substrate alone and was specific as blockade of other β1 integrin family members failed to prevent aggregation including VLA5, the canonical Fn receptor. Western blotting analysis showed a significant increase in ERK phosphorylation on Fn+B as compared to either substrate alone. VLA3 inhibition on Fn+B showed a decrease in p‐ERK while VLA5 inhibition showed a complete loss of p‐ERK. Findings indicate integrins may communicate via crosstalk pathways involving p‐ERK. NIH GM‐066194